Wie soll eine primäre Hypothyreose behandelt werden?
Statement der Britischen Schilddrüsengesellschaft gibt neue Antworten. In den erfreulich zahlreichen Kommentaren zu den Blogbeiträgen der DGE über Diagnostik und Therapie der Hypothyreose gab es se
Statement der Britischen Schilddrüsengesellschaft gibt neue Antworten.
In den erfreulich zahlreichen Kommentaren zu den Blogbeiträgen der DGE über Diagnostik und Therapie der Hypothyreose gab es sehr unterschiedliche Ansichten von Ärzten und Betroffenen. Jetzt hat die Britische Schilddrüsengesellschaft ein Statement zur primären Hypothyreose herausgegeben1, basierend auf den neuesten Leitlinien der Amerikanischen und der Europäischen Schilddrüsengesellschaft (ATA und ETA), welches von zahlreichen mit der Schilddrüse befassten Fachgesellschaften approbiert wurde. Im Folgenden soll es auszugsweise im Originaltext gebracht werden.
ATA and ETA Guidelines (Statement by the British Thyroid Association Executive Committee, Clin Endocrinol. 2016; 84(6):799-808):
L-T4 is the treatment of choice in hypothyroidism. The goal of therapy is to restore physical and psychological well-being and normalize serum TSH.
The adequacy of therapy should be determined both by clinical and biochemical assessment, and undertreatment and overtreatment should be avoided due to their detrimental health effects.
There is insufficient evidence to recommend monitoring serum T3 as a therapeutic target in hypothyroidism.
A proportion of patients on L-T4 therapy have persistent symptoms despite normal serum TSH levels. Such symptoms should be acknowledged and alternative aetiologies sought.
There is insufficient evidence that combination therapy with L-T4 and L-T3 therapy is superior to L-T4 monotherapy.
L-T4/L-T3 therapy may be considered as an ‚experimental approach‘ in compliant L-T4-treated hypothyroid patients who have persistent complaints despite reference range serum TSH values, provided they have received adequate chronic disease support and associated autoimmune diseases have been ruled out (ETA). There is currently insufficient evidence to support the routine use of such a trial of L-T4 and L-T3 outside a ‚formal clinical trial or N of 1 trial‘ (ATA).
Thyroid hormone therapy is not recommended in euthyroid individuals with (i) suggestive symptoms of hypothyroidism, (ii) obesity, (iii) depression or (iv) urticaria .
The routine use of thyroid extracts, L-T3 monotherapy, compounded thyroid hormones, iodine containing preparations, dietary supplementation, nutraceuticals and over the counter preparations are not recommended in the management of hypothyroidism.
Genetic characterization for deiodinase gene polymorphisms is not recommended as a guide to the use of combination L-T3 and L-T4 therapy in hypothyroidism.
Clinicians treating patients with hypothyroidism have an ethical obligation to avoid potential harmful therapies without proven benefits. The balance of clinical evidence regarding the efficacy of monotherapy vs combination therapy calls for further well-designed randomized controlled trials.
Statement of the British Thyroid Association Executive Committee, in line with the best principles of good medical practice and approved by other medical associations (cited in Lit.1):
It is important that high-quality, unbiased, evidence-based information about hypothyroidism is made available to patients and the public. We recognize the need to engage with patients and promote more research in hypothyroidism.
The diagnosis of primary hypothyroidism is based on clinical features of hypothyroidism supported by biochemical evidence that is elevated serum TSH together with low free T4 (overt hypothyroidism) or normal free T4 (subclinical hypothyroidism). Primary hypothyroidism should not be diagnosed in individuals with normal serum TSH who otherwise have intact pituitary function (1/++0).
The evidence in favour of narrowing the serum TSH reference range is not convincing and cannot justify the large increase in the number of healthy people that would require investigation (1/++0).
A significant proportion of healthy subjects in the community have asymptomatic chronic autoimmune thyroiditis and a significant proportion have subclinical hypothyroidism. Spontaneous recovery has been described in subjects with subclinical hypothyroidism. It is more likely in those with negative antithyroid antibodies and serum TSH levels less than 10 mU/l, and within the first 2 years after diagnosis. The higher the serum TSH value, the greater the likelihood of development of overt hypothyroidism in subjects with chronic autoimmune thyroiditis.
Synthetic L-T4 remains the treatment of choice in hypothyroidism with the aim of therapy being to restore physical and psychological well-being while maintaining normal laboratory reference range serum TSH levels (1/++0). After initiation of therapy, TSH should be monitored 6–8 weekly and the dose of L-T4 should be adjusted until a stable TSH is achieved, after which TSH can be checked 4–6 monthly, and then annually (1/+00).
It is acknowledged that a proportion of individuals on L-T4 are not satisfied with therapy and havepersistent symptoms despite a normal serum TSH. Such symptoms should be given due consideration and patients should be thoroughly evaluated for other potentially modifiable conditions. In some cases, a retrospective review of the original diagnosis of hypothyroidism may be necessary. Symptom and lifestyle management support should be provided and further dose adjustments may be required (1/+00).
Although fine tuning of serum TSH levels within the reference range may be indicated for individual patients, deliberate serum TSH suppression with high dose thyroid hormone replacement therapy (serum TSH <0·1 mU/L) should be avoided where possible as this carries a risk of adverse effects such as cardiac rhythm disorders including atrial fibrillation, strokes, osteoporosis and fracture (1/++0). As an exception, patients with a history of thyroid cancer may require deliberate suppression of serum TSH if there is a significant risk of recurrence.
For the vast majority of patients on L-T4, brand or named supplier prescribing is not considered necessary (2/+00). The Medicines and Healthcare Products Regulatory Agency (MHRA) have recently made recommendations to ensure the quality and consistency of L-T4 tablets that are on the UK Rarely, patients may require a specific brand of L-T4 to be prescribed due to intolerance of generic preparations.
Serum T3 should not be used as a therapeutic target in the management of hypothyroidism as the value of this approach is unproven (1/+00).
L-T4/L-T3 combination therapy in patients with hypothyroidism should not be used routinely, as there is insufficient evidence to show that combination therapy is superior to L-T4 monotherapy (1/++0).
Clinicians have an ethical responsibility to adhere to the highest professional standards of good medical practice rooted in sound evidence. This includes not prescribing potentially harmful therapies without proven advantages over existing treatments.
If a decision is made to embark on a trial of L-T4/L-T3 combination therapy in patients who have unambiguously not benefited from L-T4, then this should be reached following an open and balanced discussion of the uncertain benefits, likely risks of over-replacement and lack of long-term safety data. Such patients should be supervised by accredited endocrinologists with documentation of agreement after fully informed and understood discussion of the risks and potential adverse consequences. Many clinicians may not agree that a trial of L-T4/L-T3 combination therapy is warranted in these circumstances and their clinical judgement must be recognized as being valid given the current understanding of the science and evidence of the treatments (2/+00).
The serum TSH reference range in pregnancy is 0·4–2·5 mU/l in the first trimester and 0·4–3·0 mU/l in the second and third trimesters or should be based on the trimester-specific reference range for the population if available. These reference ranges should be achieved where possible with appropriate doses of L-T4 preconception and most importantly in the first trimester (1/++0). L-T4/L-T3 combination therapy is not recommended in pregnancy (1/+00).
There is no convincing evidence to support routine use of thyroid extracts, L-T3 monotherapy, compounded thyroid hormones, iodine containing preparations, dietary supplementation and over the counter preparations in the management of hypothyroidism (1/+00).
In der Originalpublikation1 sind die in Fragen und die Empfehlungen, mit Quelle (ATA, ETA) und Evidenzgrad angeführt. Diese Arbeit wird gewiss jeder Endokrinologe, insbesondere wenn er sich besonders mit der Schilddrüse beschäftigt, mit Gewinn lesen. Zumeist drückt sie wohl ohnedies seine Meinung aus, aber er kann Argumente finden, wenn manche Patienten anders behandelt werden möchten. Dass eine Hypothyreose nicht immer einfach zu behandeln ist und Normalisierung des Stoffwechsels nicht immer mit Wohlbefinden gleichzusetzen ist, zeigt eine neue dänische Arbeit2.
1 Onyebuchi Okosieme et al: Management of Primary Hypothyroidism Statement by the British Thyroid Association Executive Committee; Clin Endocrinol. 2016; 84(6):799-808
2 Winther KH, Cramon P, Watt T, Bjorner JB, Ekholm O, Feldt-Rasmussen U, et al. Disease-specific as well as generic quality of life is widely impacted in autoimmune hypothyroidism and improves during the first six months of levothyroxine therapy. PLoS ONE. 2016;11(6):e0156925.