There is controversy regarding whether to treat subtle abnormalities of thyroid function in infertile female patients. This guideline document reviews the risks and benefits of treating subclinical hypothyroidism in female patients with a history of infertility and miscarriage, as well as obstetric and neonatal outcomes in this population.

Subclinical hypothyroidism (SCH) is characterized by elevated thyroid-stimulating hormone (TSH) and normal free thyroxine levels. The Korean Thyroid Association recently issued a guideline for managing SCH, which emphasizes Korean-specific TSH diagnostic criteria and highlights the health benefits of levothyroxine (LT4) treatment. A serum TSH level of 6.8 mIU/L is presented as the reference value for diagnosing SCH. SCH can be classified as mild (TSH 6.8 to 10.0 mIU/L) or severe (TSH >10.0 mIU/L), and patients can be categorized as adults (age <70 years) or elderly (age ≥70 years), depending on the health effects of LT4 treatment. An initial increase in serum TSH levels should be reassessed with a subsequent measurement, including a thyroid peroxidase antibody test, preferably 2 to 3 months after the initial assessment. While LT4 treatment is not generally recommended for mild SCH in adults, it is necessary for severe SCH in patients with underlying coronary artery disease or heart failure and it may be considered for those with concurrent dyslipidemia. Conversely, LT4 treatment is generally not recommended for elderly patients, regardless of SCH severity. For those SCH patients who are prescribed LT4 treatment, the dosage should be personalized, and serum TSH levels should be regularly monitored to maintain the optimal LT4 regimen.

Subclinical hypothyroidism (SCH) is a common endocrine problem with prevalence estimates between 4% and 20%. Symptoms are often non-specific but can substantially affect well-being leading to repeated medical consultations. The effect of thyroid hormone replacement therapy (THRT) in patients with SCH remains uncertain. Current guidelines, limited by the lack of high-quality evidence, have been controversial with limited adherence in clinical practice.
Three-round modified Delphi method to establish consensus regarding diagnosis and treatment of individuals with SCH with and without affective disorder or anxiety, conducted with clinicians from three specialties, general practice, endocrinology and psychiatry, and two countries, Sweden and the United Kingdom.
Sixty clinicians, 20 per specialty, were recruited. Fifty-three (88%) participants completed all three rounds. The participants reached consensus on five of the 26 practice statements that (a) repeated testing was required for the diagnosis of subclinical hypothyroidism, (b) antibody screening should usually occur, and (c and d) antibody screening would strengthen the indication for thyroid hormone replacement therapy in both individuals with or without affective disorder or anxiety. The participants disagreed with (e) a requirement of a TSH threshold ≥ 20 mIU/L for thyroid hormone replacement therapy start. Psychiatrists and GPs but not endocrinologists, agreed that there was a frequent discrepancy between laboratory results and clinical symptoms, and disagreed that testing for thyroid dysfunction was overused in patients presenting with depression or anxiety, or fatigue.
In many aspects, attitudes toward diagnosing and treating SCH remain diverse. The inability of our Delphi panel to achieve consensus on most items and the disagreement with a TSH ≥ 20 mIU/L threshold for treatment suggest that the concept of SCH may need rethinking with a better understanding of the hypothalamic-pituitary-thyroid physiology. Given that the scientific evidence is currently not conclusive, guidelines in this area should not be taken as definitive.

Persistent symptoms in patients treated for hypothyroidism are common. Despite more than 20 years of debate, the use of liothyronine for this indication remains controversial, as numerous randomised trials have failed to show a benefit of treatment regimens that combine liothyronine (T3) with levothyroxine over levothyroxine monotherapy. This consensus statement attempts to provide practical guidance to clinicians faced with patients who have persistent symptoms during thyroid hormone replacement therapy. It applies to non-pregnant adults and is focussed on care delivered within the UK National Health Service, although it may be relevant in other healthcare environments. The statement emphasises several key clinical practice points for patients dissatisfied with treatment for hypothyroidism. Firstly, it is important to establish a diagnosis of overt hypothyroidism; patients with persistent symptoms during thyroid hormone replacement but with no clear biochemical evidence of overt hypothyroidism should first have a trial without thyroid hormone replacement. In those with established overt hypothyroidism, levothyroxine doses should be optimised aiming for a TSH in the 0.3-2.0 mU/L range for 3 to 6 months before a therapeutic response can be assessed. In some patients, it may be acceptable to have serum TSH below reference range (e.g. 0.1-0.3 mU/L), but not fully suppressed in the long term. We suggest that for some patients with confirmed overt hypothyroidism and persistent symptoms who have had adequate treatment with levothyroxine and in whom other comorbidities have been excluded, a trial of liothyronine/levothyroxine combined therapy may be warranted. The decision to start treatment with liothyronine should be a shared decision between patient and clinician. However, individual clinicians should not feel obliged to start liothyronine or to continue liothyronine medication provided by other health care practitioners or accessed without medical advice, if they judge this not to be in the patient\'s best interest.

Subclinical hypothyroidism (SCH) is diagnosed when serum thyroid stimulation hormone (thyrotropin; TSH) levels are above the reference range, accompanied by levels of free thyroxine within its reference range. The management of SCH remains a diagnostic and therapeutic challenge despite many years of research relating to its epidemiology, aetiology, effectiveness of treatment and safety. European Thyroid Association (ETA) guidelines for the management of SCH were published almost a decade ago. This narrative review summarizes the clinical literature relating to SCH and outcomes since the publication of these guidelines. Clinical evidence emerging during the previous decade generally supports the view that SCH is associated with adverse outcomes to an extent that is intermediate between euthyroidism and overt hypothyroidism although evidence that treatment with thyroid hormone replacement is beneficial is lacking. Accordingly, the rationale for the recommendations for intervention in the ETA guidelines based on the age of the patient, level of serum TSH, symptoms and comorbidities remains valid today.

Interest in potential adverse outcomes associated with maternal subclinical hypothyroidism (normal free T4, elevated thyroid-stimulating hormone (TSH)) has increased significantly over recent years. In turn, the frequency of maternal thyroid function testing has risen, despite universal thyroid function screening not being recommended, leading to a marked increase in referrals to obstetric endocrinology clinics. In 2017 the American Thyroid Association revised their diagnostic and management guidelines. Although welcome, these new guidelines contain recommendations that may cause confusion in clinical practice.
To ensure uniform practice in the diagnosis and management of subclinical hypothyroidism in pregnancy across all Melbourne public hospitals.
Endocrinology and obstetric representatives from all Melbourne public hospital networks reviewed the 2017 American Thyroid Association guidelines and other relevant literature to develop a consensus for diagnosing and treating subclinical hypothyroidism during pregnancy in Melbourne. The consensus guidelines were then referred to the Endocrine Society of Australia for comment and endorsement.
Consensus was achieved and the guidelines were endorsed by the Council of the Endocrine Society of Australia. Trimester and assay-specific TSH reference intervals derived from healthy local populations should be used, where available. When unavailable, a TSH cut-off of 4 mU/L (replacing the previously recommended 2.5 mU/L) should be used to initiate treatment, irrespective of thyroid auto-antibody status. The recommended starting dose of levothyroxine is 50 μg daily, with a therapeutic TSH target of 0.1-2.5 mU/L. Levothyroxine should generally be ceased after delivery, with some exceptions. Hospitals will ensure smooth transfer of care back to the woman\'s general practitioner with clear documentation of pregnancy thyroid management and a recommended plan for follow-up.
Fewer women will be classified as having subclinical hypothyroidism during pregnancy, which is likely to lead to reductions in emotional stress, hospital visits, repeated blood tests and financial costs. Uniform clinical practice will occur across Melbourne.

OBJECTIVE: Central hypothyroidism (CeH) is a rare form of hypothyroidism characterized by insufficient thyroid stimulation due to disturbed pituitary and/or hypothalamic functioning. Due to its origin and the whole clinical context, CeH represents a challenging condition in clinical practice as it is characterized by suboptimal accuracy of clinical and biochemical parameters for diagnosis and management. Since no expert consensus or guidance for this condition is currently available, a task force of experts received the commitment from the European Thyroid Association (ETA) to prepare this document based on the principles of clinical evidence.
METHODS: The task force started to work in February 2017 and after a careful selection of appropriate references (cohort studies, case reports, expert opinions), a preliminary presentation and live discussion during the 2017 ETA meeting, and several revision rounds, has prepared a list of recommendations to support the diagnosis and management of patients with CeH.
RESULTS: Due to the particular challenges of this rare condition in the different ages, the target users of this guidance are pediatric and adult endocrinologists. Experts agreed on the need to recognize and treat overt CeH at all ages, whereas treatment of milder forms may be dispensable in the elderly (> 75 years).
CONCLUSIONS: Despite the lack of randomized controlled clinical trials, the experts provide 34 recommendations supported by variable levels of strength that should improve the quality of life of the affected patients and reduce the metabolic and hormonal consequences of inadequate management.

The 2017 American Thyroid Association guidelines for the diagnosis and management of thyroid disease during pregnancy and the postpartum were published six years after the previous ones. They provide comprehensive clinical recommendations for the whole spectrum of thyroid diseases, as well as for optimal iodine intake during pregnancy, postpartum, and lactation. The present position statement mainly regards the recommended flow chart for therapeutic decision making in pregnant women being diagnosed with subclinical hypothyroidism. Here, we comment on the major biochemical and clinical situations and the corresponding therapeutic recommendations. In particular, we welcome the critical revision of the thyrotropin (TSH) reference range in pregnancy, and we agree that there is no need to treat thyroid peroxidase antibody-negative women with a serum TSH ranging from 2.5 μIU/mL to the upper limit of the reference range. This recommendation will hopefully reduce the huge proportion of healthy pregnant women in whom, according to the previous guidelines, levothyroxine therapy had to be initiated. On the other hand, we are concerned with the recommendation to only \"consider treatment\" in thyroid peroxidase antibody-negative pregnant women with a serum TSH ranging from the upper limit of the reference range to 10.0 μIU/mL. This is because thyroid antibodies may be falsely negative during gestation, and serum negative chronic autoimmune thyroiditis is a well-known clinical entity even outside pregnancy. Based on these and other arguments, we recommend treatment with levothyroxine in pregnant women with TSH levels ranging between the upper limit of the reference range and 10.0 μIU/mL independently from their thyroid antibody status.

OBJECTIVE: This study sought to examine the effect of changing TSH threshold recommendations from 2.5 to 4 mIU/L before fertility therapy on the prevalence of early gestational subclinical hypothyroidism (SCH) (TSH2 >2.5 mIU/L) and to evaluate implications on progression to clinical pregnancy (defined as detection of cardiac activity on ultrasound).
METHODS: A retrospective chart review was performed in an academic fertility clinic on all patients with a measured pre-treatment TSH (TSH1) and positive beta-human chorionic gonadotropin following fertility treatment. The study assessed the effect of TSH2 on ongoing pregnancy, both in patients newly diagnosed with SCH and in patients previously receiving LT4, stratified by initial TSH.
RESULTS: Of 482 women included in the study, baseline TSH (TSH1) was <2.5 mIU/L in 333 women (69%) and 2.5-4 mIU/L in 64 women (13.2%). Eighty-five women were taking LT4 at baseline (17.6%). Among women with a TSH1 between 2.5 and 4 mIU/L, the corresponding TSH in early pregnancy (TSH2) was <2.5 mIU/L in 35 women (55%). Overall, there was no difference in progression to clinical pregnancy between women with a TSH2 of 2.5-4 mIU/L compared with women with a TSH2 <2.5 mIU/L (OR 0.70; 95% CI 0.44-1.09). Similarly, when excluding women taking LT4 at baseline, there was no difference in progression to clinical pregnancy (OR 0.90; 95% CI 0.28-2.86).
CONCLUSIONS: Rate of progression to clinical pregnancy was equivalent between women with an early pregnancy TSH (TSH2) <2.5 and women with a TSH2 of 2.5-4.0 mIU/L. Our findings support initiating LT4 in early pregnancy, as opposed to pre-pregnancy if the TSH remains above cut-off because there does not appear to be a difference in in early pregnancy outcomes if treatment is delayed.

Subclinical hypothyroidism (SCH) should be considered in two categories according to the elevation in serum thyroid-stimulating hormone (TSH) level: mildly increased TSH levels (4.0-10.0 mU/l) and more severely increased TSH value (>10 mU/l). An initially raised serum TSH, with FT4 within reference range, should be investigated with a repeat measurement of both serum TSH and FT4, along with thyroid peroxidase antibodies, preferably after a 2- to 3-month interval. Even in the absence of symptoms, replacement therapy with L-thyroxine is recommended for younger patients (<65-70 years) with serum TSH >10 mU/l. In younger SCH patients (serum TSH <10 mU/l) with symptoms suggestive of hypothyroidism, a trial of L-thyroxine replacement therapy should be considered. For such patients who have been started on L-thyroxine for symptoms attributed to SCH, response to treatment should be reviewed 3 or 4 months after a serum TSH within reference range is reached. If there is no improvement in symptoms, L-thyroxine therapy should generally be stopped. Age-specific local reference ranges for serum TSH should be considered in order to establish a diagnosis of SCH in older people. The oldest old subjects (>80-85 years) with elevated serum TSH ≤10 mU/l should be carefully followed with a wait-and-see strategy, generally avoiding hormonal treatment. If the decision is to treat SCH, then oral L-thyroxine, administered daily, is the treatment of choice. The serum TSH should be re-checked 2 months after starting L-thyroxine therapy, and dosage adjustments made accordingly. The aim for most adults should be to reach a stable serum TSH in the lower half of the reference range (0.4-2.5 mU/l). Once patients with SCH are commenced on L-thyroxine treatment, then serum TSH should be monitored at least annually thereafter.