A 35-year-old woman presents with progressive fatigue, weight gain, cold
intolerance, constipation, dry skin, and menstrual irregularities. She reports
gradually increasing neck fullness. On examination, she has a diffuse, firm,
non-tender goiter, dry skin, bradycardia, and delayed relaxation of the deep
tendon reflexes. Laboratory investigations show elevated TSH, low free T4, and
positive anti-thyroid peroxidase (anti-TPO) antibodies. What is the diagnosis?
The diagnosis is Hashimoto thyroiditis (chronic autoimmune
thyroiditis).
1. Definition
1. Hashimoto
thyroiditis is a chronic autoimmune inflammatory disease of the thyroid
gland.
2. It
is characterized by immune-mediated destruction of thyroid tissue,
eventually leading to hypothyroidism.
3. It
is a leading cause of primary hypothyroidism and the most common cause
in many iodine-sufficient populations.
4. It
is more common in women.
2. Etiology / Risk Factors
1. Autoimmune
destruction of the thyroid gland
2. Genetic
predisposition:
1.
Family history of autoimmune thyroid disease
2.
Certain HLA and immune-regulatory gene associations
3. Environmental
and clinical associations:
1.
Female sex
2.
Increasing age
3.
Excess iodine exposure may contribute in susceptible
individuals
4. Associated
autoimmune diseases:
1.
Type 1 diabetes mellitus
2.
Celiac disease
3.
Pernicious anemia
4.
Addison disease
5.
Vitiligo
6.
Rheumatoid arthritis
3. Pathophysiology
1. Loss
of immune tolerance to thyroid antigens
2. Activation
of autoreactive T lymphocytes
3. Immune-mediated
destruction of thyroid follicular cells
4. Formation
of thyroid autoantibodies:
1.
Anti-thyroid peroxidase (anti-TPO) antibodies
2.
Anti-thyroglobulin (anti-Tg) antibodies
5. Progressive
thyroid destruction reduces thyroid hormone production, eventually resulting in
primary hypothyroidism
6. Reduced
thyroid hormone levels cause loss of negative feedback
7. Increased
pituitary TSH secretion
8. Histology
classically shows:
1.
Dense lymphocytic infiltration
2.
Germinal center formation
3.
Destruction and atrophy of thyroid follicles
4.
Hürthle cell change
4. Clinical Features
4.1 General Features
1. Fatigue
2. Weight
gain
3. Cold
intolerance
4. Lethargy
5. Reduced
exercise tolerance
4.2 Gastrointestinal Features
1. Constipation
2. Reduced
appetite
4.3 Skin and Hair Features
1. Dry,
coarse skin
2. Hair
loss
3. Brittle
hair
4. Reduced
sweating
4.4 Cardiovascular Features
1. Bradycardia
2. Reduced
cardiac output
3. Diastolic
hypertension may occur
4.5 Neurological / Musculoskeletal Features
1. Slowed
mentation
2. Depression
3. Muscle
weakness
4. Muscle
cramps
5. Delayed
relaxation of deep tendon reflexes
6. Carpal
tunnel syndrome
4.6 Reproductive Features
1. Menstrual
irregularities
2. Menorrhagia
3. Infertility
4. Reduced
libido
4.7 Thyroid Findings
1. Diffuse,
firm, non-tender goiter is typical
2. A
goiter is not always present
3. The
thyroid may become atrophic later in the disease
5. Diagnosis
5.1 Thyroid Function Tests
1. Overt
primary hypothyroidism
1.
↑ TSH
2.
↓ Free T4
2. Subclinical
hypothyroidism
1.
↑ TSH
2.
Normal free T4
3. Early
disease may be euthyroid.
5.2 Thyroid Antibodies
1. Anti-TPO
antibodies
1.
Most useful antibody marker
2.
Present in most patients with Hashimoto thyroiditis
2. Anti-thyroglobulin
antibodies
1.
May also be present
2.
Less sensitive than anti-TPO antibodies
3. Positive
antibodies support an autoimmune etiology, but antibody
positivity alone does not necessarily indicate hypothyroidism.
4. Anti-TPO
antibody levels should not be serially monitored.
5. Once
the diagnosis is established, follow thyroid function, particularly TSH,
rather than antibody titers.
5.3 Imaging
1. Thyroid
ultrasound is not routinely required when the diagnosis is clear
clinically and biochemically.
2. Ultrasound
is useful when:
1.
Thyroid nodules are present
2.
The gland is asymmetric
3.
Structural thyroid disease is suspected
3. Typical
ultrasound findings:
1.
Heterogeneous echotexture
2.
Reduced echogenicity
5.4 Fine-Needle Aspiration
1. Fine-needle
aspiration is not routinely required for Hashimoto thyroiditis.
2. It
is indicated when a suspicious thyroid nodule or other concerning structural
abnormality requires evaluation.
6. Differential Diagnosis
1. Other
causes of primary hypothyroidism
2. Iodine
deficiency or excess
3. Drug-induced
hypothyroidism
4. Post-radioiodine
hypothyroidism
5. Post-thyroidectomy
hypothyroidism
6. Subacute
thyroiditis
7. Postpartum
thyroiditis
8. Graves
disease
9. Infiltrative
thyroid disease
10. Thyroid
malignancy when a suspicious nodule or asymmetric enlargement is present
7. Management
7.1 Core Principle
1. Replace
deficient thyroid hormone, normalize TSH, and monitor clinically and
biochemically
7.2 Levothyroxine Therapy
1. Levothyroxine
(T4) is the treatment of choice for hypothyroidism.
2. In
otherwise healthy younger adults requiring full replacement:
1.
Approximate full-replacement dose: 1.6
µg/kg/day
3. Dose
requirements vary according to residual thyroid function and patient
characteristics.
4. In
patients who are overweight or obese, ideal body weight or lean body
mass may provide a more appropriate basis for dose estimation than actual body
weight.
5. The
dose should be individualized according to:
1.
Age
2.
Body weight and body composition
3.
Severity and duration of hypothyroidism
4.
Cardiovascular disease
5.
Pregnancy
6. In
older patients or patients with coronary artery disease:
1.
Start with a lower dose
2.
Titrate gradually
7.3 How to Take Levothyroxine
1. Take
levothyroxine consistently on an empty stomach.
2. Common
approaches include:
1.
Taking it 30 to 60 minutes before breakfast
2.
Taking it at bedtime, several hours after the last meal
3. Separate
levothyroxine from substances that impair its absorption, particularly:
1.
Iron
2.
Calcium
3.
Certain antacids and interacting medications
7.4 Subclinical Hypothyroidism
1. Treatment
is individualized.
2. In
nonpregnant adults, persistent TSH ≥10 mIU/L is an important threshold
for considering levothyroxine treatment.
3. Some
guidelines, including NICE, recommend confirming TSH ≥10 mIU/L on two
separate measurements approximately 3 months apart before initiating
treatment in adults.
4. When
TSH is elevated but below 10 mIU/L, management should consider:
1.
Age
2.
Presence and severity of hypothyroid symptoms
3.
Persistence or progression of TSH elevation
4.
Evidence of underlying autoimmune thyroid disease,
including anti-TPO positivity
5.
Cardiovascular disease or cardiovascular risk
6.
Individual patient context and preference
5. In
symptomatic adults younger than 65 years with persistently elevated TSH below
10 mIU/L, a time-limited therapeutic trial of levothyroxine may be
considered, depending on the guideline and clinical context.
6. Pregnancy
and preconception require separate pregnancy-specific treatment thresholds and
targets.
7.5 Euthyroid Hashimoto Thyroiditis
1. Patients
with positive thyroid antibodies but normal TSH and free T4 generally
do not require levothyroxine.
2. Periodic
thyroid function monitoring is appropriate.
3. Repeated
measurement of thyroid antibody titers is not required.
8. Hashitoxicosis
1. Some
patients develop a transient hyperthyroid phase called hashitoxicosis.
2. It
results from the release of preformed thyroid hormone from damaged
thyroid follicles, rather than increased hormone synthesis.
3. Features
may include:
1.
Palpitations
2.
Tremor
3.
Heat intolerance
4.
Weight loss
4. It
is usually self-limited.
5. Symptomatic
treatment with a beta-blocker may be used when appropriate.
6. Antithyroid
drugs are generally not useful because thyroid hormone synthesis is
not increased.
7. If
differentiation from Graves disease is uncertain:
1.
Measure TSH receptor antibodies (TRAb/TSI)
2.
Consider thyroid radionuclide uptake and scanning when
appropriate
8. Graves
disease is associated with increased thyroid hormone synthesis and typically
increased uptake, whereas destructive thyroiditis usually has low
thyroid uptake.
9. Monitoring
1. Measure
TSH approximately 4 to 6 weeks after starting levothyroxine or after a
dose adjustment.
2. Adjust
the dose according to TSH and the clinical response.
3. Once
stable:
1.
Monitor TSH periodically, commonly every 6 to
12 months
4. Reassess
earlier when:
1.
Symptoms change
2.
Pregnancy occurs
3.
A major weight change occurs
4.
Interacting medications are started or stopped
5. Avoid
excessive levothyroxine replacement.
6. Do
not routinely monitor anti-TPO titers.
10. Pregnancy
1. Thyroid
hormone requirements commonly increase during pregnancy.
2. Pregnancy
requires pregnancy-specific TSH targets and treatment thresholds.
3. Women
already taking levothyroxine generally require an early increase of
approximately 20% to 30% in their levothyroxine dose once pregnancy is
confirmed.
4. Thyroid
function should be monitored closely, typically about every 4 weeks
during the first half of pregnancy.
5. Further
monitoring is guided by gestational age, thyroid function results, and
treatment adjustments.
6. Adequate
maternal thyroid hormone levels are important for maternal and fetal health.
11. Complications
1. Overt
hypothyroidism
2. Dyslipidemia
3. Cardiovascular
disease
4. Infertility
5. Pregnancy
complications
6. Neuropsychiatric
manifestations
7. Myxedema
coma in severe untreated hypothyroidism
8. Increased
risk of primary thyroid lymphoma, although the absolute risk
remains low
9. Red
flags for thyroid lymphoma include:
1.
Rapidly enlarging thyroid or neck mass
2.
Dysphagia
3.
Dyspnea
4.
Hoarseness
5.
New cervical lymphadenopathy
12. Associated Conditions
1. Type
1 diabetes mellitus
2. Celiac
disease
3. Pernicious
anemia
4. Addison
disease
5. Vitiligo
6. Other
autoimmune disorders
13. Key Clinical Insight
1. Fatigue
+ weight gain + cold intolerance + constipation + firm non-tender goiter + ↑
TSH + ↓ free T4 + anti-TPO antibodies = Hashimoto thyroiditis
References
1. Caturegli
P, De Remigis A, Rose NR. Hashimoto thyroiditis: clinical and
diagnostic criteria. Autoimmunity Reviews.
2014;13(4-5):391-397. doi:10.1016/j.autrev.2014.01.007.
2. Jonklaas
J, Bianco AC, Bauer AJ, et al. Guidelines for the Treatment of
Hypothyroidism: Prepared by the American Thyroid Association Task Force on
Thyroid Hormone Replacement. Thyroid. 2014;24(12):1670-1751.
doi:10.1089/thy.2014.0028.
3. National
Institute for Health and Care Excellence. Thyroid disease: assessment
and management. NICE guideline NG145. London: National Institute for
Health and Care Excellence.