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Subclinical Hyperthyroidism

Article in Endocrine Practice · February 2021

DOI: 10.1016/j.eprac.2021.02.002

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 Endocrine Practice 27 (2021) 254e260

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Review Article

Subclinical Hyperthyroidism: A Review of the Clinical Literature

Karen Tsai, MD 1, 2, Angela M. Leung, MD, MSc 1, 2, *
1
Division of Endocrinology, Diabetes, and Metabolism; Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, California
2
Division of Endocrinology, Diabetes, and Metabolism; Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, California

a r t i c l e i n f o a b s t r a c t

Article history: Subclinical hyperthyroidism (SCHyper) is a biochemical diagnosis characterized by a decreased serum
Available online 13 February 2021 thyroid-stimulating hormone (TSH) and normal serum thyroxine (T4) and triiodothyronine (T3) con-
centrations. Because SCHyper can be resolved, it is recommended to repeat serum TSH, T3, and T4
Keywords: concentrations in 3 to 6 months before confirming a diagnosis of SCHyper to consider treatment. Pro-
subclinical hyperthyroidism posed grading systems distinguish between mild (TSH, 0.1-0.4 mIU/L) and severe SCHyper (TSH, <0.1
hyperthyroidism
mIU/L) and are used alongside patients’ age and the presence of risk factors and symptoms to guide
thyroid-stimulating hormone
treatment. Appropriate evaluation includes an investigation of the underlying cause and assessment of
thyrotropin
thyroid hormones
an individual’s risk factors to determine the necessity and type of treatment that may be recommended.
SCHyper may be associated with increased risks of cardiovascular-related adverse outcomes, bone loss,
and in some studies, cognitive decline. Treatment may include observation without therapy, initiation of
antithyroid medications, or pursuit of radioiodine therapy or thyroid surgery. Considerations for treat-
ment include the SCHyper etiology, anticipated long-term natural history of the condition, potential
benefits of correcting the thyroid dysfunction, and risks and benefits of each treatment option. The
purpose of this overview is to provide a guide for clinicians in evaluating and managing SCHyper in the
routine clinical practice.
Published by Elsevier Inc. on behalf of the AACE.

Clinical Vignette ng/dL (reference range, 0.8-1.7 ng/dL), and free triiodothyronine of
333 pg/dL (reference range, 222-383 pg/dL). In this article, we re-
A 66-year-old woman with a history of prediabetes and osteo- view the evidence and recommendations regarding the evaluation
porosis presented with intermittent palpitations and a 5-lb unin- and treatment of this patient’s clinical presentation.
tentional weight loss over the past month. She was not taking any
medications or supplements. Her family history consists of Graves’ Definition and Diagnosis
disease in her mother. On exam, she had normal vital signs and a
palpable and diffusely enlarged thyroid gland. Her laboratory re- Subclinical hyperthyroidism (SCHyper) is a biochemical diag-
sults revealed a serum thyroid-stimulating hormone (TSH) level of nosis characterized by normal serum thyroxine (T4) and triiodo-
0.01 mIU/L (reference range, 0.3-4.7 mIU/L), free thyroxine of 1.2 thyronine (T3) levels in a setting of decreased serum TSH
concentrations regardless of the presence or absence of symptoms.
In contrast, overt hyperthyroidism is characterized by an elevated
Abbreviations: ATA, American Thyroid Association; AACE, American Association serum T3 and/or T4 with decreased TSH levels. A proposed grading
of Clinical Endocrinologists; BMD, bone mineral density; CI, confidence interval; system distinguishes mild from severe SCHyper, according to the
COVID-19, coronavirus disease-2019; ETA, European Thyroid Association; HR, haz- degree of TSH reduction (mild SCHyper, TSH 0.1-0.4 mIU/L; severe
ard ratio; hCG, human chorionic gonadotropin; IRR, age-adjusted incidence rate; SCHyper, TSH <0.1 mIU/L).1
MMI, methimazole; RAI, radioiodine; SCHyper, subclinical hyperthyroidism; TSH,
thyroid-stimulating hormone; T4, thyroxine; T3, triiodothyronine; TMNG, toxic
multinodular goiter; TRAb, thyrotropin receptor antibody; TBII, TSH-binding Epidemiology
inhibitory immunoglobulin.
* Address correspondence and reprint requests to Dr. Angela M. Leung, Endo-
crinology, Diabetes, and Metabolism, Department of Medicine, 11301 Wilshire Blvd
The prevalence of SCHyper is dependent on age, ethnicity, sex,
(111D), Los Angeles, CA 90073. and iodine intake.2-4 In a United States’ population survey, 1.3% of
E-mail address: [email protected] (A.M. Leung). individuals aged
12 years were found to have hyperthyroidism

https://doi.org/10.1016/j.eprac.2021.02.002
1530-891X/Published by Elsevier Inc. on behalf of the AACE.
K. Tsai and A.M. Leung Endocrine Practice 27 (2021) 254e260

(SCHyper, 0.7%; overt hyperthyroidism, 0.5%).3 In the TEARS Scot- normal serum TSH levels as a part of non-thyroidal illness,
tish study, SCHyper was described at a prevalence of 0.63% and an depending on the phase of the illness.20 Other causes of decreased
incidence of 29 per 100 000 individuals.4 Furthermore, this longi- TSH levels that are not necessarily indicative of the endogenous
tudinal study reported that 6.1% of individuals with SCHyper pro- causes of SCHyper include hypothalamic and pituitary dysfunction,
gressed to overt hyperthyroidism in the first year; of the remainder, TSH-b gene mutations, spurious thyroid function tests caused by
only 0.5% to 0.7% developed overt hyperthyroidism over 7 years.4 In the interference of heterophile antibodies and paraproteins, and
addition, the majority (63%) remained persistently SCHyper the use of medications that include biotin, metformin, dopamine
without treatment, while 36% spontaneously returned to normal agonists, glucocorticoids, dopamine, and somatostatin
serum thyroid function, especially those with TSH concentrations analogues.11,21,22,23,24,25
between 0.1 and 0.4 mIU/L, over the 7-year follow-up.4 In general, Since the identification of severe acute respiratory syndrome
there is a higher prevalence of SCHyper among women, older in- coronavirus 2 in 2019, which sparked the coronavirus disease-2019
dividuals, and those living in iodine-deficient regions.2-5 Blacks and (COVID-19) pandemic, there has been a growing research assessing
smokers have been noted to have lower biochemical TSH values, the effects of the infection on serum thyroid function. One retro-
which may not represent true SCHyper biologically, but instead spective study reported a high prevalence of SCHyper in COVID-19
reflect a leftward shift in the TSH setpoint in these groups.3,6 patients associated with high circulating levels of interleukin-6,
due to a proposed mechanism of destructive thyroiditis.26 This is
Etiologies of SCHyper consistent with another study that noted 10 of 191 COVID-19 pa-
tients developed SCHyper due to thyroiditis.27 Several series have
The causes of SCHyper can be distinguished between endoge- described lower than normal TSH values among those with COVID-
nous versus exogenous etiologies of hyperthyroidism and transient 19, and those with severe infections have particularly decreased
versus persistent sources of the thyroid dysfunction. The exogenous TSH values.26-29 These patterns may be due to possible direct viral
causes of SCHyper may be intentional, for example as part of the effects on TSH-secreting cells in the pituitary gland, disruption in
treatment of some differentiated thyroid cancers, although may the pituitary-thyroid feedback loops from COVID-19 and its thera-
also be surreptitious, if thyroid hormone is used by some in an pies, or non-thyroidal illness.26-29
attempt for weight loss. Thyroid hormone replacement, such as
levothyroxine, liothyronine, or desiccated thyroid extract, in pa- Diagnostic Evaluation of SCHyper
tients treated for hypothyroidism may also overestimate physio-
logic needs and may result in SCHyper.7,8 The endogenous causes of Recommendations for the diagnostic evaluation of SCHyper vary
SCHyper include thyroiditis, toxic thyroid nodules, toxic multi- among major medical societies. For example, the U.S. Preventive
nodular goiter (TMNG), and Graves’ disease. Graves’ disease may be Services Task Force recommends refraining from serum thyroid
more prevalent in younger patients, while TMNG is more common function screening in nonpregnant, asymptomatic patients,
in older patients.9,10 whereas the American Association of Clinical Endocrinologists
Despite being transient, SCHyper may last up to 3 to 6 months, (AACE) advocates for an aggressive case-finding approach to
depending on the etiology.11 SCHyper can be transient as a result of identify individuals who are most likely to have thyroid dysfunc-
the treatment of overt hyperthyroidism with radioiodine (RAI) tion and will likely benefit from its treatment.30,31 Furthermore, the
therapy or antithyroid medications during the transition to American Thyroid Association (ATA) and European Thyroid Asso-
euthyroidism. It may also be transient due to the various forms of ciation (ETA) recommend monitoring younger subjects <65 years
thyroiditis (ie, subacute thyroiditis, painless thyroiditis, postpartum old at regular 6- to 12-month intervals and correction of SCHyper
thyroiditis, lithium-induced thyroiditis, immune-related thyroiditis only if the TSH is persistently <0.1 mIU/L.11,32 The ETA further
related to the use of immune checkpoint inhibitors, and recommends a treatment consideration in this specific group when
amiodarone-induced thyroiditis).12-15 Other medications known to the serum thyrotropin receptor antibody (TRAb) titer is persistently
cause thyroiditis include interferon-a, interleukin-2, and tyrosine detectable, and/or thyroid RAI uptake is increased.32
kinase inhibitors.11 The clinical presentation of SCHyper can vary from the absence
It is significant to note, however, that SCHyper does not warrant of symptoms to mild symptoms of hyperthyroidism, such as
treatment in some cases. Differentiating true SCHyper from other arrythmias, heat intolerance, insomnia, increased appetite, diar-
causes of low TSH concentration will help guide the next steps in its rhea, weight loss, hair loss, diaphoresis, abnormal menses, and
workup and whether treatment is indicated. During pregnancy, hand tremors. The initial serologic workup following the finding of
human chorionic gonadotropin (hCG) levels are particularly SCHyper consists of repeating the thyroid function tests. These
elevated in early gestation and in those with hyperemesis grav- should include the measurement of serum TSH and free and/or
idarum. Owing to the structural homology between hCG and TSH, total T4 and T3 concentrations. If the biochemical abnormalities are
hCG in pregnant women can stimulate TSH receptors to increase confirmed, the titers of serum thyroid antibodies, such as TRAb,
thyroid hormone production, resulting in a decreased TSH level TSH-binding inhibitory immunoglobulin (TBII), thyroid-stimulating
that may be confused as SCHyper.16 The majority of women with immunoglobulin, and thyroglobulin antibody, may be obtained if
hyperemesis gravidarum will have spontaneous remission of these an autoimmune thyroid etiology is suspected. Serum thyroid-
abnormal thyroid function tests when vomiting ceases in stimulating immunoglobulin, TBII, and TRAb are highly sensitive
pregnancy.17 and specific, cost efficient, and readily available; test positivity
Additionally, iodine is frequently found in high amounts in some would suggest a diagnosis of Graves’ disease as the cause of the
vitamins and supplements and commonly as a component of SCHyper.11,33 An elevated serum thyroglobulin level would support
radiologic contrast media. Acute or chronic iodine exposure, a diagnosis of thyroiditis, whereas a low thyroglobulin level would
especially in those with pre-existing thyroid disease or other risk suggest an exogenous thyroid hormone use, which can be inten-
factors, can induce SCHyper.18 A Brazilian study reported a positive tional or unintentional.14 Other lab tests that help in the diagnosis
association between SCHyper and panic disorders, although a of thyroiditis include elevations in erythrocyte sedimentation rate,
negative association between SCHyper and anxiety disorders, C-reactive protein, white blood cell count, and thyroid peroxidase
suggesting a link between psychiatric disorders and thyroid antibody. Moreover, a decreased hemoglobin level may be detected
dysfunction.19 Critically ill patients may also present with low to as part of the complete blood count.11 Because iodine is
255
K. Tsai and A.M. Leung Endocrine Practice 27 (2021) 254e260

predominantly renally excreted, an elevated spot urine iodine association between SCHyper and other cardiovascular disorders or
concentration can be helpful in ruling in recent iodine exposure as a mortality.39 A study of community-dwelling adults aged
65 years
cause of the SCHyper.34 in the U.S. (n ¼3233) similarly reported no increased risk of all-
Moreover, imaging can be pursued to help differentiate between cause death among those with SCHyper (HR, 1.08; 95% CI, 0.72-
etiologies and guide the treatment of SCHyper if indicated. A thy- 1.62) after adjusted analyses.39 Risks for coronary heart disease
roid ultrasound with Doppler flow can be used to detect hyper- mortality, heart failure, and atrial fibrillation may be dependent on
vascularity that is suggestive of Graves’ disease. Thyroid the severity of SCHyper and are higher in those with serum TSH
scintigraphy with 123I or 99MTc can be obtained to assess thyroid levels <0.10 mIU/L than in those with lower degrees of
gland activity. Low scintigraphic uptake would suggest thyroiditis SCHyper.38,46
or exogenous thyroid hormone use, while focally increased uptake The association between SCHyper and stroke is less well un-
is consistent with toxic thyroid nodule(s), and diffuse increased derstood. One meta-analysis showed no evidence supporting an
uptake is diagnostic of Graves’ disease. increased risk of stroke in those with SCHyper.43,47 Other studies
Because SCHyper can spontaneously resolve, it is recommended have reported that patients with SCHyper were at an increased risk
to repeat serum TSH, T3, and T4 concentrations in 3 to 6 months of functional disability, worsened prognosis, and unsuccessful
before confirming a diagnosis of SCHyper and considering treat- reperfusion after ischemic stroke compared with euthyroid
ment.11 Patients at a high risk of SCHyper-related complications individuals.48,49
may have thyroid function tests performed earlier (eg, 2-6
weeks).11 In case of abnormal thyroid function tests resulting from Bone Loss
the use of biotin-streptavidin immunoassays, ATA recommends
abstaining from biotin for at least 2 days before repeating the blood Thyroid hormone also plays major roles in the regulation of
tests.11 bone metabolism. Excess thyroid hormone leads to increased
osteoclastic activity and net bone loss. Overt hyperthyroidism is a
Adverse Effects Of SCHyper well-established cause of secondary osteoporosis and increases the
risk of fractures.50
Cardiovascular Effects However, data on the association between SCHyper and its ef-
fects on bone health remain inconsistent. In a recent meta-analysis
Thyroid hormone is significant in the regulation of cardiac of 13 prospective cohort studies with 70 298 individuals (median
function, and SCHyper may adversely affect cardiac morphology and age, 64 years; 61.3% women), SCHyper was found to be associated
function.35 SCHyper is associated with increased heart rate, atrial with an increased risk of hip (HR ¼ 1.36; 95% CI, 1.13-1.64) and any
arrhythmias, and especially atrial fibrillation, atrial and ventricular fracture defined as any non-vertebral or vertebral fracture (HR ¼
premature beats, elevated nocturnal arterial blood pressure, 1.28; 95% CI, 1.06-1.53), particularly in those with serum TSH levels
increased QT interval dispersion, and heart rate variability.35-41 One <0.10 mIU/L and those with endogenous etiologies of SCHyper,
population-based cohort study of 586 460 individuals (mean age, such as Graves’ disease, TMNG, and toxic thyroid nodules.51 Simi-
50.2 ± 16.9 [standard deviation {SD}] years; 39% men) with SCHyper larly, another study found a significant bone loss in the lumbar
showed increasing incidence rates of atrial fibrillation with spine and hips of postmenopausal women who had SCHyper on
decreasing TSH levels (1.16 % if TSH 0.1-0.2 mIU/L vs 1.41% if TSH <0.1 suppressive thyroid hormone therapy.52 Other prospective studies
mIU/L).37 Cardiac structural changes associated with SCHyper have found no associations between SCHyper and its effects on
include an increased left ventricular mass due to an increase of bone turnover among older men and on bone mineral density
septal and posterior wall thickness, potentially causing diastolic (BMD) measurements among healthy middle-aged adults.53,54 In
dysfunction.35,36 Tadic et al has described the echocardiographic one large prospective study with 3338 men aged 70-89 years, there
changes that can occur in some individuals with SCHyper as having was no association of hip fracture and SCHyper (P ¼ .254).53
a notably impaired right atrial and right ventricular function in both Other data demonstrate that the treatment of SCHyper can have
systole and diastole as well as a hyperkinetic cardiovascular state positive effects on the bone and may prevent the continued loss of
that leads to hemodynamic overload.42 bone mass up to 2% per year.41,55 Faber et al similarly examined the
Several studies have shown that SCHyper is associated with effects of RAI therapy on BMD in 16 postmenopausal women with
increased all-cause mortality, major adverse cardiovascular events SCHyper from multinodular goiter. The authors noted an increased
mostly due to heart failure, and adverse prognoses in those with spinal BMD of 1.9% and 1.5% at 1- and 2-year follow-up, respec-
pre-existing heart failure as well as increased coronary heart dis- tively, and an increased hip BMD of 2.3% and 1.7% at 1- and 2-year
ease mortality and events.38,43,44,45 In a systematic review of 52 674 follow-up, respectively.55 Mudde et al studied 16 postmenopausal
individuals (median age, 59 years; 58.5% women) with a median women with endogenous SCHyper from multinodular goiter and
follow-up of 8.8 years and a total follow-up of 501 922 person- noted that in those treated with methimazole (MMI, n ¼ 8), mean
years, the overall age- and sex-adjusted hazard ratios (HRs) for BMD was increased and continued bone loss at the distal forearm
those with SCHyper compared with euthyroid patients was 1.24 for was halted compared with untreated controls.56 In this study,
total mortality (95% confidence interval [CI], 1.06-1.46), 1.29 for despite BMD gains, bone turnover serum markers did not signifi-
coronary heart disease mortality (95% CI, 1.02-1.62), 1.21 for coro- cantly change.56
nary heart disease events (95% CI, 0.99-1.46), and 1.68 for incident
atrial fibrillation (95% CI, 1.16-2.43).38 In a retrospective Danish Dementia and Cognitive Decline
cohort study of 563 700 individuals (mean age, 48.6 ± 18.2 [SD]
years; 39% men), all-cause mortality was increased among those Evidence supporting the association between SCHyper and
with SCHyper (age-adjusted incidence rate, 15.3 per 1000 person- cognitive decline is equivocal. A meta-analysis suggested that there
years; incidence rate ratio [IRR], 1.23; 95% CI, 1.16-1.30) compared may be an elevated risk of dementia and Alzheimer disease asso-
with euthyroid patients.43 In this analysis, SCHyper subjects also ciated with SCHyper; however, the thyroid dysfunction is not
had an elevated risk of major adverse cardiovascular events (IRR, associated with faster neurocognitive decline as assessed by Mini-
1.09; 95% CI, 1.02-1.16) and heart failure (IRR, 1.20; 95% CI, 1.10- Mental State Examination results 57. Other studies suggest associ-
1.31).43 On the other hand, another prospective study found no ations between SCHyper and cognitive impairment, overall
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K. Tsai and A.M. Leung Endocrine Practice 27 (2021) 254e260

Table 1
Recommendations for the Management of Subclinical Hyperthyroidism (adapted from 2016 ATA11 and 2011 AACE guidelines14)

TSH 0.1-0.4 mIU/La (Mild SCHyper) TSH <0.1 mIU/L (Severe SCHyper)

Aged <65 yb
Asymptomatic Monitor Consider treating
Asymptomatic with risk factorsc Consider treating Consider treating
Symptomatic Consider treating Treat
Aged ≥65 y
Asymptomatic Consider treating Treat
Asymptomatic with risk factorsc Consider treating Treat
Symptomatic Consider treating Treat

Abbreviations: ATA ¼ American Thyroid Association; AACE ¼ American Association of Clinical Endocrinologists; SCHyper ¼ subclinical hyperthyroidism.
a
0.4 mIU/L is the lower limit of most reference ranges
b
Please see special considerations for pregnant women in the text.
c
Risk factors¼ cardiac disease, osteoporosis, and menopausal women not on estrogens or bisphosphonates.

dementia, vascular dementia, and Alzheimer disease in men.58,59 (Table 1).11,14 Treatment should also be initiated in individuals aged
Among older adults, those with serum TSH levels <0.10 mIU/L <65 years, with or without hyperthyroid symptoms, whose serum
were at a higher risk of developing dementia and increased TSH levels remain persistently <0.1 mU/L (Table 1).11,14
cognitive decline than those with more mildly decreased serum In 2015, ETA published similar guidelines regarding the treat-
TSH levels.60 However, another prospective study of men and ment of SCHyper.32 The guidelines recommend treatment in those
women aged 70-82 years (n ¼ 5154) found no associations between aged >65 years with serum TSH levels <0.1 mIU/L and a strong
SCHyper and cognitive impairment or decline.61 consideration for treatment in those aged >65 years with serum
TSH levels between 0.1 and 0.39 mIU/L, especially in those with
Other Adverse Effects pre-existing cardiovascular disease or comorbidities, such as pe-
ripheral arterial disease, stroke, diabetes, or renal failure.32 The
There is growing research on the association of other clinical guidelines recommend that the decision to treat should be indi-
outcomes and SCHyper. From limited literature, SCHyper is corre- vidualized for those aged <65 years, especially if the individual has
lated with metabolism and increases the risk of hyperglycemia and persistent or overt symptoms of hyperthyroidism, and in patients
decreased serum total cholesterol, LDL-cholesterol, and HDL- with serum TSH <0.1 mIU/L and cardiovascular-related comorbid-
cholesterol levels.62,63 In addition, SCHyper can impair the quality ities.32 These recommendations state that treatment in younger
of life as a result of an increased adrenergic state due to heat asymptomatic patients is not warranted. Such individuals can be
intolerance, sweating, palpitations, hand tremors, and anxiety; monitored with serial serum thyroid function tests due to the low
such symptoms may warrant treatment and symptom alleviation risk of transition into overt hyperthyroidism and likely sponta-
with cardioselective beta blockers.64 neous remission of the SCHyper. Supporting reasons for the early
treatment of SCHyper in appropriate candidates include avoiding
SCHyper in Pregnancy the progression to overt hyperthyroidism and increased total
mortality, cardiovascular mortality, atrial fibrillation, and fracture
In pregnancy, SCHyper is relatively uncommon and typically risks in untreated individuals.11,32,72,73
does not warrant treatment, in contrast to overt hyperthyroidism.
Studies suggest that SCHyper occurs in 1.7% of singleton pregnan- Treatment of SCHyper
cies and may be more common in African American and/or parous
patients.65 SCHyper does not appear to be associated with Options for the treatment of SCHyper follow the same principles
increased risks of maternal, obstetric, or neonatal morbidities, as overt hyperthyroidism and include thionamides (ie, MMI or
when compared to euthyroid pregnant women, and instead may propylthiouracil),131I-radioactive therapy, and thyroid surgery.
even have decreased risks of gestational hypertension.65,66 Several Adrenergic symptoms can be treated with cardioselective beta
recommendations suggest that SCHyper in pregnancy does not blockers, such as propranolol, atenolol, or metoprolol, and titrated
necessarily require treatment and may be monitored.65-67 How- to achieve the goal heart rate of <90 beats/min.11 One should
ever, SCHyper during 4 to 8 weeks of pregnancy has also been re- closely monitor blood pressure in individuals managed with beta
ported to be associated with a decreased incidence of abortion, blockers due to the side effect of hypotension. The type of beta
although is a risk factor for preeclampsia and placental abruption.68 blocker, especially in those with polypharmacy or history of
It should be noted that serum TSH concentrations may vary noncompliance, should be an additional consideration (ie, atenolol
across different ethnicities; thus, mildly abnormal values may be can be dosed once a day, whereas propranolol is dosed every 4-6 h).
observed during pregnancy and may not suggest a clinically sig- MMI is a reasonable treatment option in appropriate in-
nificant SCHyper.69-71 Future research is needed in this arena to dividuals, especially in young patients in whom remission is likely
better understand the clinical effects of SCHyper in pregnant and those with mild disease. One study suggests that MMI of up to
women and the fetus as well as in women during preconception. over 8 years of use was as safe and effective as RAI therapy in
treating TMNG.74 In older adults, both RAI therapy and low-dose
Indications for the Treatment of SCHyper MMI can be used safely and effectively in the treatment of
SCHyper.75 Another study assessing long-term thionamide use has
Guidelines from ATA and AACE suggest that individuals with suggested that the remission of Graves’ hyperthyroidism occurs
SCHyper should be treated when serum TSH is <0.1 mIU/L in those mostly after 4-11 years of treatment and those with a disappear-
aged
65 years with cardiac risk factors, heart disease, or osteo- ance of serum TBII titers within 5 years or without TBII fluctuation
porosis; postmenopausal women who are not on estrogens or or enlargement of goiter may suggest a better prognosis.76 This is
bisphosphonates; and in individuals with hyperthyroid symptoms consistent with the findings from a systematic review and
257
K. Tsai and A.M. Leung Endocrine Practice 27 (2021) 254e260

meta-analysis that favored longer treatment with antithyroid the repeated blood tests are similar, the appropriate further
medications, which showed a remission rate of 16% for each year of workup should be pursued, which may include serum thyroid an-
continued treatment (95% CI, 10%-27%).77 Another prospective tibodies, thyroid ultrasound, and thyroid scintigraphy. If an
randomized controlled trial with 302 patients with Graves’ hyper- endogenous etiology for the SCHyper is confirmed from this eval-
thyroidism found that the administration of low-dose MMI for 60- uation, the patient’s older age (≥65 years), presence of hyperthy-
120 months safely and effectively treats Graves’ hyperthyroidism, roid symptoms, and osteoporosis would support treatment. A
with much higher rates than those attained by the conventional discussion to guide the choice of whether a thionamide should be
duration of 18-24 months.78 initiated or 131I radioactive therapy or thyroid surgery pursued
If treatment is not initiated, trending serum thyroid function should take into account the etiology of the SCHyper, anticipated
tests can be performed every 3 months, especially in those in whom long-term natural history of the condition, potential benefits of
there is a high chance of spontaneous resolution of the biochemical correcting the thyroid dysfunction, and the risks and benefits of
abnormality.11 each treatment option.
For lactating mothers with SCHyper managed with a thio-
namide, the medication should be administered just after breast-
Disclosure
feeding, which provides a 3- to 4-h interval prior to subsequent
lactation.79,80 Pregnancy should be deferred for 6 months in those
The authors have no multiplicity of interest to disclose.
who have received 131I treatment due to the risk of fetal/neonatal
hypothyroidism.79 The use of 131I is contraindicated during lacta-
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