Page 989 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPTEr 70 Autoimmune Thyroid Diseases 955

Except for individuals with known heart disease or the very old, 1–4 months. During the thyrotoxic phase, preformed thyroid
a full, weight­related replacement dose (≈1.6 µg/kg/day) should hormone stores are released from the thyroid follicles, leading
be started. Once the patient is on a stable dose, thyroid function to thyrotoxicosis, which may be severe. The hypothyroid phase
should be assessed annually to ensure that the patient continues follows when these preformed stores are exhausted and the thyroid
to receive the appropriate dose. Some commonly prescribed has become depleted of hormones. In about 90% of cases this
medications, such as calcium and iron supplements, and proton hypothyroidism is transient, but in some cases, it never resolves.
pump inhibitors interfere with the absorption of L­T 4 , and patients
should be advised to take these at least 4 hours before or after POSTPARTUM THYROIDITIS
their L­T 4 to ensure maximum absorption.
Postpartum thyroiditis (PPT) is a common endocrine condition
Subclinical Hypothyroidism that manifests within 1 year following pregnancy. It affects
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Although the need to treat individuals with overt AH is universally between 5% and 10% of women in the general population. PPT
accepted, it is unclear whether thyroid hormone replacement is is classically a biphasic disorder, consisting of a period of transient
beneficial in individuals with persistent subclinical hypothyroidism thyrotoxicosis (median onset 12–14 weeks post partum) followed
(serum TSH raised, but fT 4 and fT 3 within the normal reference by a period of transient hypothyroidism (median onset 18–20
range on at least two separate occasions). Progression to overt weeks post partum); however, a monophasic (thyrotoxicosis or
hypothyroidism from this state occurs in about 2% of individuals hypothyroidism alone) or reversed biphasic (hypothyroidism
per year who are TPO antibody negative, rising to 5% per year followed by thyrotoxicosis) pattern can also occur. During
if antibodies are present. Persistent subclinical hypothyroidism pregnancy, there is a state of relative immune tolerance, followed
has been associated with a number of markers of cardiac and by a rebound in immune function following delivery, coinciding
vascular dysfunction in observational studies, including left with the occurrence of PPT. The presence of thyroid autoantibod­
ventricular diastolic dysfunction, increased vascular resistance, ies and a lymphocytic infiltrate on thyroid biopsy supports an
and atherosclerosis. A randomized controlled study is now autoimmune basis for this condition. 29
underway to determine whether thyroid hormone replacement Clinically, the thyrotoxic phase of PPT is often mild, resulting
can be used to improve cardiovascular outcomes in patients with in symptoms of fatigue and irritability, which can be misdiagnosed
persistent subclinical hypothyroidism. 28 as postnatal depression. If the thyrotoxic episode is short, it may
even go unnoticed. Neck pain is not a feature. Women with
CLINICaL PEarLS PPT who are thyrotoxic may benefit from a beta­blocker, such
as propranolol, for symptom relief. Antithyroid drugs are not
Management of Persistent Subclinical effective, as the thyrotoxicosis is caused by release of preformed
Hypothyroidism thyroid hormones. Following the episode of thyroid dysfunction,
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10–20% of women remain permanently hypothyroid. In women
• If thyroid-stimulating hormone (TSH) is elevated, immediate treatment who have had PPT and then recovered, an annual assessment
should be offered: of thyroid function is recommended, as their risk of long­term
• In pregnancy 29
• Preconception, if planning a pregnancy hypothyroidism is considerable. In those women who return
• If TSH is elevated but <10 mIU/L, a trial of treatment can be offered: to being euthyroid, there is a 75% risk of PPT in subsequent
• To individuals with convincing symptoms of hypothyroidism pregnancies and a 50% risk of permanent hypothyroidism at
• If TSH is >10 mIU/L, treatment should be offered: 7 years. 30
• To individuals under the age of 70 years
• To individuals over the age of 70 years if there is a clear history of
hypothyroid symptoms or there are significant risk factors for TRANSLATIONAL RESEARCH
cardiovascular disease.
ON THE HOrIZON
FUTURE DEVELOPMENTS New Approaches to Therapy of Graves Disease
The genetics of AH remain understudied considering its frequency • Novel immunotherapeutic agents for Graves orbitopathy
as the commonest autoimmune disease in humans. Considerable • Anti–thyroid-stimulating hormone receptor (TSH-R) blocking antibodies
for control of hyperthyroid Graves disease
work remains to be done on whether treatment of subclinical • Small molecule TSH receptor antagonists for management of hyper-
hypothyroidism is beneficial. Given the insidious nature of the thyroidism in Graves disease
development of AH, it remains a good target for a preventative
immunotherapeutic intervention, if a safe and economic treatment
can be found. The major challenge of the next 5–10 years is to take novel
immunotherapeutic agents, including “biologicals” that have
OTHER FORMS OF THYROIDITIS been developed for rheumatic disorders into the clinical arena
for autoimmune thyroid diseases. The primary target of these
The term thyroiditis relates to conditions resulting in inflammation efforts should be GO, which remains a disfiguring condition,
of the thyroid gland. A number of etiologies have been described, often with substantial functional impairment of vision and
including infection, radiation exposure, drugs, and autoimmune associated low quality of life. Two randomized controlled trials
factors. A common pattern to the natural history of several of B­lymphocyte–depleting agents have yielded conflicting results,
thyroiditides is frequently seen, involving an initial thyrotoxic and therefore other powerful agents need to be investigated as
phase of 1–3 months, followed by a rapid drop in serum thyroid this remains a disorder with no wholly satisfactory treatment.
hormones and a transient hypothyroid phase, often lasting another Early diagnosis of GO and development of markers that predict