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Abstract Background Thyroid hormones are key determinants of health and well-being. Normal thyroid function is defined according to the standard 95% confidence interval of the disease-free population. Such standard laboratory reference intervals are widely applied in research and clinical practice, irrespective of age. However, thyroid hormones vary with age and current reference intervals may not be appropriate across all age groups. In this review, we summarize the recent literature on age-related variation in thyroid function and discuss important implications of such variation for research and clinical practice. Main text There is now substantial evidence that normal thyroid status changes with age throughout the course of life. Thyroid stimulating hormone (TSH) concentrations are higher at the extremes of life and show a U-shaped longitudinal trend in iodine sufficient Caucasian populations. Free triiodothyronine (FT3) levels fall with age and appear to play a role in pubertal development, during which it shows a strong relationship with fat mass. Furthermore, the aging process exerts differential effects on the health consequences of thyroid hormone variations. Older individuals with declining thyroid function appear to have survival advantages compared to individuals with normal or high-normal thyroid function. In contrast younger or middle-aged individuals with low-normal thyroid function suffer an increased risk of adverse cardiovascular and metabolic outcomes while those with high-normal function have adverse bone outcomes including osteoporosis and fractures. Conclusion Thyroid hormone reference intervals have differential effects across age groups. Current reference ranges could potentially lead to inappropriate treatment in older individuals but on the other hand could result in missed opportunities for risk factor modification in the younger and middle-aged groups. Further studies are now needed to determine the validity of age-appropriate reference intervals and to understand the impact of thyroid hormone variations in younger individuals.

Hypothyroidism is common throughout the world and readily diagnosed with thyroid function tests. Management should be straightforward but appears not to be the case. Thyroid hormone replacement with levothyroxine monotherapy is the standard treatment which is effective in the majority of cases. However, 10–15% of patients established on levothyroxine do not feel their health is entirely restored and some patients prefer the addition of liothyronine. Proponents of liothyronine argue that the ratio of T3 and T4 hormones is substantially altered on T4 monotherapy and therefore both hormones may be needed for optimal health. This remains controversial as clinical trials have not demonstrated superiority of combination therapy (levothyroxine and liothyronine) over levothyroxine monotherapy. There is now a pressing need for further studies and in particular randomized controlled trials in this area. To help design and facilitate dedicated trials and better understand thyroid hormone replacement, this review summarizes the evidence where there is established knowledge and agreement (knowns) and areas where research is lacking (unknowns). Agreements include the extent of dissatisfaction with levothyroxine monotherapy, biases in testing for hypothyroidism and prescribing levothyroxine, as well as variable thresholds for prescribing levothyroxine and challenges in liothyronine dosing. The review will also highlight and summarize the unknowns including the long-term safety profile of liothyronine, and potential biomarkers to identify individuals who might benefit most from combination therapy.

Universal thyroid screening in pregnancy is a key debate in thyroidology and obstetrics. It is well-established that thyroid hormones are essential for maintaining pregnancy and optimal fetal development. Thyroid dysfunction is common in women of child-bearing age and also results in substantial adverse obstetric and child neurodevelopmental outcomes. Furthermore, thyroid dysfunction is readily diagnosed with reliable blood tests and easily corrected with inexpensive and available treatments. Screening only high-risk patients appears to miss the majority of cases and economic models show that compared to high-risk screening, universal screening is cost effective even if only overt hypothyroidism was assumed to have adverse obstetric effects. As a result, several countries now implement universal screening. Opponents of universal thyroid screening argue that asymptomatic borderline thyroid abnormalities such as subclinical hypothyroidism and isolated hypothyroxinemia form the bulk of cases of thyroid dysfunction seen in pregnancy and that there is a lack of high quality evidence to support their screening and correction. This review critically appraises the literature, examines the pros and cons of universal thyroid screening using criteria laid down by Wilson and Jungner. It also highlights the growing evidence for universal thyroid screening and indicates the key challenges and practicalities of implementation.

An 82-year-old female with known hypothyroidism was admitted to hospital after being found on the floor. On examination, she was unkempt, confused, bradycardic, hypothermic, and barely arousable. Initial biochemistry revealed a thyroid stimulating hormone (TSH) of >100 mU/L and free thyroxine (FT4) level of 1.5 pmol/L which supported a diagnosis of myxoedema coma. She was resuscitated and commenced on liothyronine, levothyroxine, and hydrocortisone and some improvement was made. It became apparent that she was hiding and spitting out her oral levothyroxine including levothyroxine elixir. Given the need for prompt alternative control, we sought advice from international experts where intramuscular levothyroxine was recommended. She was managed from day 50 onwards with intramuscular levothyroxine 200 mcg once a week, which was subsequently increased to 500 mcg. Thyroid function normalized and she made continual cognitive and physical progress and was discharged to a rehabilitation hospital. Her intramuscular levothyroxine was stopped and she was subsequently restarted on oral levothyroxine, with a plan for on-going close monitoring of her thyroid function. This report highlights the potential to use intramuscular levothyroxine in individuals with severe hypothyroidism arising from poor compliance with levothyroxine treatment or other potential causes such as impaired absorption.

Context: Optimal thyroid status in pregnancy is essential in reducing the risk of adverse outcomes. The management of hyperthyroidism in women of reproductive age poses unique challenges and it is unclear how preconception treatment strategies impact on thyroid status in subsequent pregnancy. Objective: We aimed to determine trends in the management of hyperthyroidism before and during pregnancy and to assess the impact of different preconception treatment strategies on maternal thyroid status. Methods: We utilized the Clinical Practice Research Datalink database to evaluate all females aged 15-45 years with a clinical diagnosis of hyperthyroidism and a subsequent pregnancy (January 2000 to December 2017). We compared thyroid status in pregnancy according to preconception treatment, namely, (1) antithyroid drugs up to or beyond pregnancy onset, (2) definitive treatment with thyroidectomy or radioiodine before pregnancy, and (3) no treatment at pregnancy onset. Results: Our study cohort comprised 4712 pregnancies. Thyrotropin (TSH) was measured in only 53.1% of pregnancies, of which 28.1% showed suboptimal thyroid status (TSH >4.0 mU/L or TSH <0.1 mU/L plus FT4 >reference range). Pregnancies with prior definitive treatment were more likely to have suboptimal thyroid status compared with pregnancies starting during antithyroid drug treatment (odds ratio 4.72, 95% CI 3.50-6.36). A steady decline in the use of definitive treatment before pregnancy was observed from 2000 to 2017. One-third (32.6%) of first trimester carbimazole-exposed pregnancies were switched to propylthiouracil while 6.0% of propylthiouracil-exposed pregnancies switched to carbimazole. Conclusion: The management of women with hyperthyroidism who become pregnant is suboptimal, particularly in those with preconception definitive treatment, and needs urgent improvement. Better thyroid monitoring and prenatal counseling are needed to optimize thyroid status, reduce teratogenic drug exposure, and ultimately reduce the risk of adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Background:Myxedema coma is the extreme manifestation of hypothyroidism, typically seen in patients with severe biochemical hypothyroidism. Its occurrence in association with subclinical hypothyroidism is extremely unusual. We describe a patient with subclinical hypothyroidism who developed clinical manifestations of myxedema coma.Summary:A 47-year-old woman presented to our endocrine clinic with complaints of fatigue and biochemical findings of subclinical hypothyroidism. She was started on treatment with thyroxine (T4) but remained unwell and was later admitted to hospital with hormone profile showing persisting subclinical hypothyroidism (elevated thyrotropin and normal free T4 [FT4] and free triiodothyronine [FT3]): FT4 10.7 pmol/L (reference range 10.3–24.5), FT3 2.7 pmol/L (reference range 2.67–7.03), and thyrotropin 6.09 mU/L (reference range 0.4–4.0). She subsequently developed hypothermia (temperature 33.2°C), circulatory collapse, and coma. Biochemical profile showed hyponatremia, elevated creatinine phosphokinase, metabolic acidosis, and renal failure. An echocardiogram revealed a moderate-sized pericardial effusion. We diagnosed myxedema coma and started treatment with intravenous T3. She responded dramatically with improvement in level of consciousness and normalization of metabolic parameters. We found no explanation other than hypothyroidism to account for the presentation. Adrenocorticotrophic hormone (ACTH) stimulation tests excluded adrenal insufficiency, and serum gonadotrophins were within the normal reference range. FT4 estimation by equilibrium dialysis excluded analytical interference, and molecular analysis for the thyroid hormone receptor β gene associated with thyroid hormone resistance was negative.Conclusions:To the best of our knowledge this is the first report of myxedema coma in a patient with subclinical hypothyroidism. The reason for normal thyroid hormone levels is unclear but may reflect deviation from a higher pre-morbid set-point. The case highlights the importance of careful clinical evaluation in patients with disparate clinical and laboratory findings. [ABSTRACT FROM AUTHOR]