Новости эндокринологии, записная книжка

[ELENA_VLAD]

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Background
Women positive for thyroid peroxidase antibodies (TPO-Ab) have a higher risk of recurrent pregnancy loss. Evidence on whether levothyroxine treatment improves pregnancy outcomes in women who are TPO-Ab positive women with recurrent pregnancy loss is scarce. The aim of this study was to determine if levothyroxine increases live birth rates in women who were TPO-Ab positive with recurrent pregnancy loss and normal thyroid function.
Methods
The T4LIFE trial was an international, double-blind, placebo-controlled, phase 3 study done in 13 secondary and tertiary hospitals in the Netherlands, one tertiary hospital in Belgium, and one tertiary hospital in Denmark. Women (18–42 years) who were TPO-Ab positive, had two or more pregnancy losses, and had a thyroid stimulating hormone (TSH) concentration within the institutional reference range were eligible for inclusion. Women were excluded if they had antiphospholipid syndrome (lupus anticoagulant, anticardiolipin IgG or IgM antibodies, or β2-glycoprotein-I IgG or IgM antibodies), other autoimmune diseases, thyroid disease, previous enrolment in this trial, or contraindications for levothyroxine use. Before conception, women were randomly assigned (1:1) to receive either levothyroxine or placebo orally once daily. The daily dose of levothyroxine was based on preconception TSH concentration and ranged from 0·5–1·0 μg/kg bodyweight. Levothyroxine or placebo was continued until the end of pregnancy. The primary outcome was live birth, defined as the birth of a living child beyond 24 weeks of gestation measured in the intention-to-treat population. The trial was registered within the Netherlands Trial Register, NTR3364 and with EudraCT, 2011-001820-39.
Results
Between Jan 1, 2013, and Sept 19, 2019, 187 women were included in the study: 94 (50%) were assigned to the levothyroxine group and 93 (50%) were assigned to the placebo group. The trial was prematurely stopped when 187 (78%) of the 240 predefined patients had been included because of slow recruitment. 47 (50%) women in the levothyroxine group and 45 (48%) women in the placebo group had live births (risk ratio 1·03 [95% CI 0·77 to 1·38]; absolute risk difference 1·6% [95% CI –12·7 to 15·9]). Seven (7%) women in the levothyroxine group and seven (8%) in the placebo group reported adverse events, none of them were directly related to the study procedure.
Interpretation

Compared with placebo, levothyroxine treatment did not result in higher live birth rates in euthyroid women with recurrent pregnancy loss who were positive for TPO-Ab. On the basis of our findings, we do not advise routine use of levothyroxine in women who are TPO-Ab positive with recurrent pregnancy loss and normal thyroid function.

[ghrh44]

Независимая от ТТГ и свТ4 роль антител в феномене потери беременности была известна давно. Именно поэтому АТА рекомендует тироксин у женщин с ТТГ >10, но без антител, но у женщин с ТТГ 4-10, но с антителами, таки да рекомендует. Тироксин никоим образом не может повлиять на титр антител: разница в риске выкидыша 1.6% ( от -12 до +15). Поэтому смысл делания этой работы заключается в том, что хотя пользы от тироксина во втором случае от мала до нуля, но никто врача обвинить в бездеятельности не сможет:-). Адвокаты кусают локти.

[ghrh44]

Сообщение от Melnichenko

Dramatic, Durable Hair Growth With Oral JAK Inhibitor
— Oral baricitinib superior to placebo at 36 weeks in BRAVE-AA1 and BRAVE-AA2 trials
by Charles Bankhead, Senior Editor, MedPage Today March 27, 2022


BOSTON -- An oral Janus kinase (JAK) inhibitor produced significant, durable hair growth, including scalp, eyebrows, and eyelashes in patients with severe alopecia areata, according to long-term data from two randomized trials.

Almost 40% of patients achieved a Severity of Alopecia Tool (SALT) score ≤20 (total percentage of hair loss) at 52 weeks with a higher dose of baricitinib (Olumiant), and almost 30% had a SALT score ≤10. The patients had a mean SALT score >80 at baseline. Almost half of the patients had met response criteria for eyebrow and eyelash regrowth, reported Brett King, MD, PhD, of Yale School of Medicine in New Haven, Connecticut.

Эх, опубликовали бы это на год раньше, Уилл Смит не дал бы пuбличную пощёчину Крису Року на церемонии Оскара за шутку по поводу алопеции у своей жены.

Но зато, что бы народ читал в "жёлтой прессе" в очередях в супермаркетах и обсуждал в сетях? Других же важных проблем в мире нет, не так ли?

А вот не попробовать ли барицитиниб у акромегаликов? Сигнал ГР передаётся через JAK-STAT комплеkc. Забей JAK и... что будет с ИФР-1?
Очередная сумасшедшенькая идея....

[ELENA_VLAD]

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The mpact of moderately high preconception TSH levels on ovarian reserve among euthyroid infertile women undergoing ARTBackground: Thyroid dysfunction is prevalent in reproductive-aged women and has been identified as a risk factor for female infertility.
However, it remains largely unclear whether subtle thyroid dysfunction, as estimated by moderately high TSH levels within the normal range, is associated with ovarian reserve in infertile women prior to assisted reproductive technology (ART).
Methods: This cross-sectional study involved 3501 euthyroid infertile women, including 2189 women with TSH levels ≤2.5 μIU/mL and 1312 women with high-normal TSH levels (2.51-4.20 μIU/mL). Ovarian reserve markers were compared between women with low- and high-normal TSH levels. Correlation analysis and regression models were used to estimate the association of TSH levels with ovarian reserve. In addition, the association of subtle thyroid dysfunction with ovarian reserve was further evaluated after stratification for different infertility diagnoses and statuses of thyroid autoimmunity (TAI).
Results: In the total population, women with high-normal TSH levels had significantly decreased AMH concentrations (p<0.001), a lower bilateral AFC (p<0.001), and a higher prevalence of diminished ovarian reserve (DOR) (p=0.018) than women with low-normal TSH levels. The TSH levels showed a negative association with both AMH levels (r=-0.050, p=0.003) and bilateral AFC (r=-0.071, p<0.001). Furthermore, the association of high-normal TSH levels with decreased AMH and AFC was more prominent in infertile women with ovulation dysfunction (p=0.002, p=0.002), unexplained infertility (p=0.020, p=0.028), or negative TAI (both p<0.001).
Conclusions: These data suggested that subtle thyroid dysfunction was associated with DOR in infertile women prior to ART, which will add evidence that strengthens the systematic screening of TSH levels/TAI in infertile women and contribute to the discussion of specific TSH cutoff values in predicting ovarian reserve.

[FilippovaYulia]

А можно и мне поучаствовать? 28 апреля 2022 г. - новое руководство ESMO по применению системной терапии при тяжелых случаях рака щитовидной железы [Ссылки доступны только зарегистрированным пользователям ]
ESMO Clinical Practice Guideline update on the use of systemic therapy in
advanced thyroid cancer
S. Filetti, C. Durante, D. M. Hartl, Leboulleux, L.D. Locati, K. Newbold, M.G. Papotti10 & A. Berruti, on behalf of the ESMO Guidelines Committee*
Мощно пробило ностальгией... РНЦРР. Огромный этап в моей жизни, хотя и недолгий. Приятно вспомнить...
Начинали в 2017 году с сорафенибом и ленватинибом, в личном архиве есть красивые картинки редкого вида кожной сыпи на сорафенибе. Сама учила пациентов, как "выбивать" рекомендованный Москвой препарат в регионах (без зазрения совести пользуясь волгоградским опытом в сочетании с московским авторитетом).
И в какую же громаду таргетной терапии нынче оно вырастает. В помощь тераностике.

[Melnichenko]

Ну, жизнь идёт.
Новости с ENDO: кагрилинтид + семаглутид ( Ново)- ответка на тирзепатит Эли Лилли , но тут любопытен кагрилинид - это амилин и он дополнительно уменьшает опорожнение желудка

[Melnichenko]

Как страшно жить !Accidental exposure to glimepiride from adulterated medication resulting in severe hypoglycaemia
in Endocrinology, Diabetes & Metabolism Case Reports
Authors: Annabelle G Hayes1,2, Mahesh M Umapathysivam1,2, and David J Torpy1,2
View More

Sulphonylureas are insulinotropic and are not only useful in patients with diabetes but also act in non-diabetic individuals where hypoglycaemia and hyperinsulinism mimic insulinoma. We present a 63-year-old man who presented with inadvertent sulphonylurea-induced life-threatening hypoglycaemia on two occasions, resulting in hazardous and invasive investigation. Biochemistry revealed endogenous hyperinsulinaemia, with elevated serum c-peptide and insulin concentrations during symptomatic hypoglycaemia, and plasma glucose of 1.7 mmol/L. There was no history of sulphonylurea use prompting anatomical insulinoma studies to locate an insulinoma. However, a routine plasma insulinoma screen-detected glimepiride. Directed history implicated a medication taken for erectile dysfunction prior to disturbed consciousness, with alcohol. The tablets, obtained online, were analysed by mass spectrometry and contained tadalafil and dapoxetine as advertised but also contained glimepiride.

[Melnichenko]

Вот сейчас благодаря нашему кхн Виталию Иоутси - запросто исследовать состав - дЭАС в китайских травках, СМ в крови невинно гипующих и даже аналоги инсулина.
Есть технические сложности, но в целом эпоха тайных поисков под подушками и в вещах ушла в прошлое

[FilippovaYulia]

Как-то в разговоре с Галиной Афанасьевной упоминалась мудрая мысля, что было бы неплохо проверять и тех, у кого "инсулин колем, а сахара высоченные". Эту мыслю, несомненно, мыслил любой эндокринолог, которому после безвременной кончины "бабушки, которой от сахара никакой инсулин не помогал" скорбящие родственники притаскивали агромадные пакеты с этим самым нетронутым инсулином. Частенько уже изрядно просроченным. В наследство доктору, так сказать.

[Melnichenko]

Юля, по моему, эту мысль высказали Вы первой, и я на наших конференциях уже говорила, что по сути это заказ от практического здравоохранения. Во всяком случае, некомплаетность при первом типе , наверное, можно было бы доказывать по инсулину крови. Надо помозговать.

[Melnichenko]

Dexamethasone a Safe Premedication Option for Patients With Primary Aldosterone Who Are Allergic to Iodine Contrast Media
– Prednisone is the pretreatment standard, but can make AVS interpretation difficult
by Scott Harris , Contributing Writer, MedPage Today October 17, 2022

For patients allergic to iodine contrast media (ICM), dexamethasone premedication prior to adrenal venous sampling (AVS) is a safe and more effective alternative to prednisone and other approaches when classifying primary aldosteronism (PA).

That's according to recent findings published in the Journal of the Endocrine Society.

Researchers at Centre Hospitalier of the University of Montreal in Canada identified 177 patients with confirmed PA who underwent bilateral simultaneous basal and post-adrenocorticotropic hormone (ACTH) bolus AVS. A total of 7 patients (4%) with previous allergic reactions to ICM were prepared with 3 doses of 7.5 mg of dexamethasone premedication rather than the usual 50 mg of prednisone, which can pose challenges when interpreting AVS results.

No breakthrough allergic reactions occurred in the 7 patients. Despite dexamethasone administration, cortisol response to ACTH was adequate.

Study co-author, Andre Lacroix, MD, is an endocrinologist-researcher with the center. He recently discussed the study and its findings with the Reading Room. The exchange has been edited for length and clarity.

This is something of a controversial topic. Why is that the case?

Lacroix: AVS is the optimal approach to adequately subtype PA into predominantly lateralized or bilateral disease is adrenal venous sampling. However, performing AVS in patients with ICM allergy is challenging.

Limited options are available for these patients. Alternative subtyping techniques include gadolinium-based contrast media for adrenal venography, carbon dioxide as a substitute for contrast dye, and radioiodine-labeled cholesterol analogue adrenal scintigraphy.

Each of these alternatives, however, poses significant clinical or technical challenges.

We've been doing AVS for more than 30 years, and had approached the problem differently.

How does your center approach the issue, and how did that approach lead to this study?

Lacroix: Generally, for people with ICM allergies, oral premedication with glucocorticoids (usually 3 doses of prednisone 50 mg) is administered at 13, 7, and 1 hours prior to the intervention. However, in the case of AVS, this method has long been abandoned, as prednisone can interfere with cortisol assays and suppress basal cortisol levels, rendering AVS interpretation difficult.

So instead of prednisone, we use dexamethasone. The advantage of dexamethasone over prednisone, is that it does not interfere with the measurement of cortisol and blood. At the same time, glucocorticoid pretreatment has been viewed by some as insufficiently safe to prevent ICM allergy.

We decided we would review the data that we had accumulated over the years on cases of AVS in patients with a history of ICM allergy.

How would you summarize what you discovered?

Lacroix: We went back and identified seven cases in which this procedure had been done under dexamethasone suppression. We demonstrated that in all cases, the AVS was adequate, that it allowed us to identify whether the PA was unilateral or bilateral, and that patients responded adequately to surgery when it was indicated.

Simply put, we demonstrated that dexamethasone is safe and allowed confirmation that the technical aspect was accomplished.

What are the clinical messages here that you think are important to emphasize?

Lacroix: This study demonstrated that a very simple substitution of prednisone by dexamethasone is efficient, and that none of the patients had any allergic reactions.

Severe contrast media allergy is not so frequent, but when it exists, you need to have a solution to be able to perform the exam, and to be able to offer the appropriate diagnosis and course of therapy for patients.

Our essential point was that you can substitute prednisone by dexamethasone in equivalent doses, and that it is efficient, safe, and allows adequate interpretation and performance of the examination.

Clinical implications

Dexamethasone is safe and effective as a premedication alternative to prednisone for adrenal venous sampling in patients with primary aldosteronism with iodine contrast media allergies.
Dexamethasone does not interfere with test interpretation like prednisone can.
Alternative subtyping techniques, such as substituting iodine medium for gadolinium, can pose considerable technical or clinical problems.

[Melnichenko]

Fezolinetant improves vasomotor symptom severity, associated sleep disturbances
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Women taking fezolinetant for moderate to severe vasomotor symptoms experienced a reduction in symptom severity and sleep disturbances, according to data presented at the NAMS Annual Meeting.

Notably, fezolinetant (Astellas Pharma) was associated with reduced vasomotor symptoms across racial subgroups as well as across the entire study population.

Fezolinetant reduced symptoms and improved sleep disturbances among women with moderate to severe vasomotor symptoms. Source: Adobe Stock
Fezolinetant reduced vasomotor symptoms and improved sleep disturbances among women with moderate to severe vasomotor symptoms. Source: Adobe Stock
“This is really exciting because it is truly the first time that we have a treatment that is specifically targeted at what we know causes hot flashes,” Genevieve Neal-Perry, MD, PhD, a member of the Fezolinetant Scientific Advisory Committee for Astellas and chair of the department of obstetrics and gynecology at University of North Carolina School of Medicine, told Healio. “There is great opportunity to meet unmet needs for patients who can’t use hormones, such as breast cancer survivors and patients with blood clot disorders.”

Efficacy by racial group
Neal-Perry and colleagues evaluated the efficacy of the nonhormonal, investigational selective neurokinin-3 receptor agonist among Black and non-Black participants in two phase 3 studies, SKYLIGHT 1 and SKYLIGHT 2. Overall, both double-blind, placebo-controlled trials found fezolinetant — which was administered once daily in 30 mg or 45 mg doses for 12 weeks — to be efficacious and well tolerated by participants.

According to Neal-Perry, Black women experience hot flashes more frequently and over a greater length of time compared with white women and are more likely to have hot flashes before menopause.

Genevieve Neal-Perry, MD, PhD
Genevieve Neal-Perry
“And so why does this really matter?” Neal-Perry said. “It matters because we know that women who have hot flashes are more likely to have heart disease, they’re more likely to have cognitive problems in terms of being able to do daily functions because of the disruption of sleep and the impact on general quality of life.”

In total, 1,022 women took at least one dose of fezolinetant or placebo. Compared with non-Black women, Black women reported hot flashes more frequently at baseline. Black women and non-Black women following either fezolinetant regimen reported significant reductions in the frequency of hot flashes at weeks 4 and 12 compared with their counterparts taking placebo.

Additionally, compared with placebo, 45 mg fezolinetant was associated with a significant reduction in severity of vasomotor symptoms across the study population and among Black and non-Black participants at weeks 4 and 12.

These findings show that despite differences in drug metabolism between white and Black women, “fezolinetant works, it’s highly effective and race does not have an impact on its effectiveness,” Neal-Perry said.

Sleep disturbances
A second study was conducted by Marla Shapiro, MDCM, CCFP, MHSc, FRCP, FCFP, NCMP, an associate professor in the department of family and community medicine at the University of Toronto, and colleagues to identify the impact fezolinetant had on sleep disturbances associated with vasomotor symptoms. Again, the researchers used data from SKYLIGHT trials 1 and 2 for their analyses.

The Patient-Reported Outcomes Measurement Information System Sleep Disturbance – Short Form (PROMIS SD SF) 8b Total Score, Patient Global Impression of Change – Sleep Disturbance (PGI-C SD) and PGI of Severity – Sleep Disturbance (PGI-S SD) were used to assess sleep disturbances among 1,022 participants who had taken fezolinetant or placebo at least once.

Compared with placebo, women who took 45 mg fezolinetant had significant improvements in scores for sleep disturbances on all three assessments at weeks 4 and 12, according to the researchers. Among women taking 30 mg fezolinetant, significant improvements in sleep were observed at week 4 using the PROMIS SD SF and PGI-S SD, and at weeks 4 and 12 using the PGI-C SD.

“We still need to do some additional studies to understand more about who will benefit in terms of sleep,” Neal-Perry said. “[For example], is it possible that people who have more night-time hot flashes are the ones who benefit in terms of overall sleep patterns?”

[Melnichenko]

Неплохая идея
‘What’s in a name? That which we call a rose/By any other name would smell as sweet’ (Juliet,
from Romeo and Juliet by William Shakespeare). Shakespeare’s implication is that a name
is nothing but a word, and it therefore represents a convention with no intrinsic meaning.
While this may be relevant to romantic literature, disease names do have real meanings,
and consequences, in medicine. Hence, there must be a very good rationale for changing
the name of a disease that has a centuries-old historical context. A working group of
representatives from national and international endocrinology, and pediatric endocrine
societies now proposes changing the name of ‘diabetes insipidus’ to ‘arginine vasopressin
deficiency (AVP-D)’ for central etiologies, and ‘arginine vasopressin resistance (AVP-R)’ for
nephrogenic etiologies. This article provides both the historical context and the rationale
for this proposed name changing
Endocrine Connections
(2022) 11, e220378
This work is licensed under a Creative Commons
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[Ссылки доступны только зарегистрированным пользователям ] © 2022 The authors
Published by Bioscientifica Ltd
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via free access
H Arima et al. e220378
11:11
Reasons for changing a disease name
Understanding of disease processes is a dynamic field,
with rapidly evolving concepts of pathophysiology based
on emerging molecular and genetic data. Consequently,
newer understanding of pathophysiology is one of the
major reasons for renaming diseases. In endocrinology,
appreciation of hyperprolactinemia as the common
pathophysiology underlying many different clinical
situations causing galactorrhea and amenorrhea led to
the effective abandonment of many previous eponymous
names for these conditions, such as Chiari–Frommel
syndrome, Forbes–Albright syndrome and Ahumada–
del Castillo syndrome (1). A second reason is based on
historical discoveries that a previous eponymous name for
a syndrome was inappropriately attributed to an individual
who was not the first or even the most significant person
involved in the description of the syndrome (2). A
third reason is later appreciation of medically unethical
behaviors of individuals with diseases eponymously
named for them, as characterized by the renaming of
Reiter’s syndrome to ‘reactive arthritis’ and Wegener’s
granulomatosis to ‘granulomatosis with polyangiitis’,
because of the association of the eponymous physicians
with Nazi antihumanitarian crimes (3, 4). The first three
of these reasons for changing disease names make a
strong case for detaching eponyms from disease processes
whenever possible (5). However, endocrinologists would
be loathe to abandon the eponyms of Addison, Cushing,
Hashimoto and others for their unique and seminal
contributions to our understanding of endocrine disease
processes. However, yet a fourth reason for renaming
diseases is when traditional disease names lead to confusion
between pathophysiologically different processes, leading
to treatment errors and consequent adverse outcomes for
patients. This last reason represents the major impetus to
change the name of diabetes insipidus at this time.
Historical context
Before explaining the rationale for the name change, it is
instructive to review the historical context for the name of
diabetes insipidus. The polyuria and polydipsia of diabetes
were first described by Demetrius of Apameia (1st–2nd
century BC), who used the term ‘diabetes’, meaning
‘passing water like a siphon’ to describe the polyuria
characteristic of this condition. Araetus of Cappadocia
(81–138 AD) further defined the clinical characteristics of
this disease (6). Although observations that the urine was
sweet were alluded to in both Greek and Indian history, the
first documented report of the sweet character of diabetic
urine was published by the English physician Sir Thomas
Willis in 1674 (The Diabetes or Pissing Evil). However, the
differentiation between the saccharine urine of glucosuria
and the non-saccharine urine of other forms of polyuria is
attributed to the Scottish physician William Cullen, who
appended the Latin word ‘mellitus’ (sweet) to the Greek
term ‘diabetes’ to distinguish between these two types of
polyuria (7). In 1794, Johann Peter Frank first introduced
the term ‘diabetes insipidus’ to differentiate these patients
from those with diabetes mellitus (7). These terms
persisted as valid clinical descriptions without known
pathophysiology until the vasopressor and antidiuretic
actions of posterior pituitary extracts were discovered in
the late 19th and early 20th centuries, including the use
of posterior pituitary extracts to treat diabetes insipidus.
In the mid-20th century, arginine vasopressin (AVP) was
synthesized and identified as the antidiuretic hormone,
and the distinct central and nephrogenic etiologies of
diabetes insipidus were recognized and characterized (8).
Despite new knowledge of the underlying pathophysiology
of the different etiologies of diabetes insipidus by the late
20th century, no attempts were made to rename diabetes
insipidus according to the known causes of the disorder,
namely, deficiency of AVP or resistance to the receptormediated actions of AVP.

[ghrh44]

‘Эпонимические” имена болезней крайне часто основываются на национальности их “первоописателей”.
Истощенный больной с зобом, пучеглазием и тахикардией в Англии страдает от болезни Грейвса, в Германии от болезни Базедова, а в Италии от болезни Флайяни.

Во всем мире все знают о болезни Мари, которую он назвал акромегалией. Но наши итальянские коллеги упрямо зовут ее Прозопэктазия, имя, дaнное ей итальянцем Андреа Верга, описавшим ее на 20 лет раньше Мари. Лет 30 назад они даже создали на первом сабантуе -консенсусе в Кортина д’ Aмпеццо “ Propectazia Society”, членом которого №7 я являюсь ( не потому, что был одним из первых присоединившихся, a просто по алфавиту:-))
Но в Голландии даже выпустили марку с портретом Йоханнесa Вира, oписавшим акромегалию аж в 16 веке, но никакого приоритета голландцы почему-то не требуют.
Нет у них патриотизма!

Так что практически все страны тянут одеяло на себя.

Единственный противоположный случай, который я знаю, это сифилис. Во всей Европе он всегда звался “французской болезнью” но французы щедро отдали приоритет и звали его “ итальянской болезнью”. У россиян претензий к итальянцам не было, и в России он звался “ польской болезнью”:-)

Чем-то похоже на Австрию, где Бетховен считается австрийцем, а Гитлер немцем.

[Melnichenko]

In a real-world analysis of patients with thyroid eye disease treated with a full course of teprotumumab-trbw (Tepezza), only 4.9% were prescribed a second course within 2 years, maker Horizon Therapeutics said.