woensdag 28 september 2016

Daily administration of short-acting liothyronine is associated with significant triiodothyronine excursions and fails to alter thyroid-responsive parameters

Although most studies of levothyroxine-liothyronine combination therapy employ once-daily hormone administration, the kinetics of once-daily liothyronine have been studied infrequently. The aim of this study was to document both the peak and trough serum triiodothyronine (T3) levels that occur with once-daily liothyronine administration, along with changes in thyroid-responsive parameters.

Daily administration of short-acting liothyronine is associated with significant triiodothyronine excursions and fails to alter thyroid-responsive parameters
J Jonklaas, KD Burman

Participants with hypothyroidism were studied prospectively at an academic institution. Patients were switched from levothyroxine monotherapy to liothyronine monotherapy with 15 μg liothyronine for two weeks, and then continued liothyronine at doses of 30-45 μg for a further four weeks in an open-label, single-arm study. Weekly trough levels of T3 were documented. In addition, hourly T3 concentrations immediately following liothyronine tablet administration were documented for eight hours during the sixth week of therapy. Serum thyrotropin (TSH) and free thyroxine (fT4) concentrations were documented. Biochemical markers, markers of energy metabolism, anthropometric parameters, well-being, and hyperthyroid symptoms were also assessed.

Results

Mean serum TSH levels increased from 1.56 ± 0.81 mIU/L at baseline to 5.90 ± 5.74 mIU/L at two weeks and 3.84 ± 3.66 mIU/L at six weeks. Trough T3 levels decreased from 99.5 ± 22.9 to 91.9 ± 40.2 at two weeks and recovered to 96.1 ± 32.2 at six weeks. The peak T3 concentration after dosing of liothyronine during week 6 was 292.8 ± 152.3 ng/dL. fT4 levels fell once levothyroxine was discontinued and plateaued at 0.44 ng/dL at week 4. The sex hormone binding globulin (SHBG) concentration decreased at week 2 (p = 0.002). Hyperthyroid symptoms and SF36-PCS scores increased significantly at weeks 4-5 of liothyronine therapy (p = 0.04-0.005). Preference for liothyronine therapy increased from 6% to 39% over the study period.

Conclusions

Once-daily dosing of liothyronine at doses of 30-45 μg did not return serum TSH to the values seen during levothyroxine therapy. There were significant excursions in serum total and free T3 concentrations with once-daily therapy. Trials of combination therapy are likely to be associated with similar excursions, albeit of a lesser magnitude. Only the physical component score of the SF36 questionnaire and hyperthyroid symptoms changed significantly with conversion to liothyronine monotherapy. Sustained release preparations with stable serum T3 profiles may have entirely different outcomes.

vrijdag 23 september 2016

Hormoontherapie met geregistreerde of zelfbereide medicijnen?

In Nederland is onduidelijkheid ontstaan over het zelf bereiden door apothekers van levothyroxine. In de berichtgeving rond de nieuwe circulaire Handhavend optreden bij collegiaal doorleveren van eigen bereidingen door apothekers van de Inspectie voor de Gezondheidszorg (IGZ) is namelijk verwezen naar de problemen met de levering van Thyrax. Apothekers in Nederland mogen alleen medicatie bereiden indien er geen geregistreerde adequate alternatieven beschikbaar zijn. Voor Thyrax zijn deze geregistreerde alternatieven wel beschikbaar.

Compounded bioidentical hormones in endocrinology practice: an Endocrine Society Scientific Statement
N Santoro, GD Braunstein, CL Butts, KA Martin, M McDermott, JV Pinkerton

Choosing commercial or compounded medicines
RM Plotzker

In bijgaande artikelen kun je lezen dat de keus tussen het zelf bereiden door apothekers of het gebruik van geregistreerde commerciële medicijnen ook in de Verenigde Staten speelt. Artsen worden aangespoord geregistreerde medicijnen voor te schrijven. Maar ook dan kan het fout gaan. Als voorbeeld wordt Synthroid genoemd, te vergelijken met Thyrax.

Abstract

Custom-compounded bioidentical hormone therapy (HT) has become widely used in current endocrine practice, which has led to unnecessary risks with treatment. This scientific statement reviews the pharmacology and physiology of popular compounded hormones and the misconceptions associated with these therapies. The hormones reviewed include: estradiol and estrogens, progesterone and progestins, testosterone, dehydroepiandrosterone, levothyroxine and triiodothyronine.

Results

Overall, there is a general lack of standardization and quality control regarding how custom-compounded bioidentical hormones are produced and administered, leading to the possibility of overdosing, underdosing, or contamination. There is also recent evidence of patient harm and death associated with treatment, as seen with fungus-contaminated glucocorticoid preparations. With estrogen, progestin, and dehydroepiandrosterone treatments, the practice of baseline hormone measurements to replace “abnormal” hormone deficiencies has no basis in medical practice. Furthermore, there is no evidence that monitoring compounded HT with serial salivary or blood testing is effective, except in the case of thyroid hormone. Finally, no evidence supports the popularized notion that custom-compounded bioidentical hormones have fewer risks when compared with Food and Drug Administration (FDA)-approved hormone treatments.

Conclusion

The widespread availability of FDA-approved bioidentical hormones produced in monitored facilities demonstrates a high quality of safety and efficacy in trials; therefore, there is no rationale for the routine prescribing of unregulated, untested, and potentially harmful custom-compounded bioidentical HTs. Clinicians are encouraged to prescribe FDA-approved hormone products according to labeling indications and to avoid custom-compounded hormones.



woensdag 21 september 2016

86e jaarlijkse bijeenkomst American Thyroid Association

Van 21 tot 25 september vindt de jaarlijkse bijeenkomst plaats van de Amerikaanse Schildklier Associatie. Klik op de link voor alle abstracts.


Allerlei onderzoekers delen in de abstracts hun nieuwste bevindingen. Jammer genoeg draait het vaak om schildklierkanker. Aandacht voor nieuwe behandelingen van hypo- en hyperthyreoïdie zou welkom zijn.


zondag 18 september 2016

Bijzondere opties voor de behandeling van de ziekte van Graves

Dit artikel gaat in op voor- en nadelen van de huidige behandelopties van de ziekte van Graves. Denk aan schildklierremmers (block + replace en titratie), radioactief jodium en operatie. Ook aan bod komen minder bekende behandelingen zoals onder andere lithium, rituximab en jodium (lugol).

Current and emerging treatment options for Graves’ hyperthyroidism
Prakash Abraham, Shamasunder Acharya

Treatment of thyrotoxicosis
Andrei Iagaru and I. Ross McDougall

Radioiodine may be given using fixed high doses or by calculated doses following uptake studies. The risks of radioiodine including eye disease and the role of prophylactic steroid therapy are discussed. The commonly used antithyroid drugs include carbimazole, methimazole and propylthiouracil; however a number of other agents have been tried in special situations or in combination with these drugs. The antithyroid drugs may be given in high (using additional levothyroxine in a block–replace regimen) or low doses (in a titration regimen).

This review examines the current evidence and relative benefits for these options as well as looking at emerging therapies including immunomodulatory treatments such as rituximab which have come into early clinical trials. The use of antithyroid therapies in special situations is also discussed as well as clinical practice issues which may influence the choices.

Other antithyroid agents


Betablockers

Many of the symptoms of hyperthyroidism such as sweating, anxiety, tremor and palpitations are caused by increased sympathetic activity and can be controlled rapidly by beta-blockers. Propranolol in relatively high doses of over 160 mg per day can mildly inhibit conversion of T4 to T3. Once daily betablockers such as atenolol 50 to 100 mg or nadolol 40 to 80 mg can be used to improve compliance. In the absence of contraindications such as asthma, betablockers are used in the first few weeks of treating hyperthyroidism while awaiting the effect of antithyroid medications. They may also be used when antithyroid medications are withdrawn for treating with RAI. Rate-limiting calcium channel blockers may be used if there are contraindications for betablockers.

Iodine and iodine-containing compounds

These are rarely used for the rapid control of hyperthyroidism in the context of thyroid storm or in the preoperative preparation for thyroid surgery. Iodide decreases thyroid hormone synthesis by blocking iodide oxidation and organification – the Wolff–Chaikoff effect. It also inhibits thyroglobulin proteolysis and release of T4 and T3. The effect is rapid and pronounced but lasts for only a few weeks with a potential for subsequent deterioration. Iodide decreases the vascularity of the thyroid but in one controlled study had no significant influence on blood loss or perioperative course. It can be given as Lugol’s solution (8 mg of saturated iodide per drop) 3 to 5 drops 3 times a day or as a saturated solution of potassium iodide (SSKI, 50 ng of iodide per drop) 1 drop 3 times a day. Oral cholecystographic agents (sodium iopanoate and sodium ipodate) have also been used for rapidly lowering thyroid hormone levels in combination with MMI74 and may be useful in thyroid storm.

Lithium

Lithium has a role in inhibiting thyroid hormone synthesis and release. Lithium can rarely be used in patients intolerant of thionamides. It has been shown to reduce the thyroid hormone increase after thionamide withdrawal and RAI therapy in Graves’ disease.

Potassium perchlorate

This is a competitive inhibitor of iodide transport but is rarely used due to its side effects, particularly the risk of aplastic anemia with long-term use. It may be used in the context of amiodarone-induced thyrotoxicosis or while awaiting RAI in patients allergic to thionamides.

Cholestyramine

Cholestyramine decreases the enterohepatic reabsorbtion of thyroid hormones. Thyrotoxic patients have an abnormal increase of thyroid hormones in their enterohepatic circulation. Cholestyramine used in combination with PTU or MMI brought about a more rapid decline of thyroid hormones during the first month of antithyroid therapy.

Rituximab

Graves’ disease is an autoimmune B-cell mediated condition in which TSH receptor antibodies (TRAb) play an important role in the pathogenesis. A few agents are being investigated but the only agent that has entered phase II clinical studies is rituximab (RTX). This is an anti-CD20 monoclonal antibody which causes B cell depletion in the circulation as well as in target organs such as the thyroid. Due to the limited experience and costs further studies are needed before these agents are considered as possible therapies in GH.


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