Новости эндокринологии, записная книжка
 

Я пыталась сеять разумное и даже где- то вечное на совершенно поразительном по скоплению своеобразных личностей форуме Врачи РФ, но потерпела фиаско и сейчас попробую свою записную книжку ( что показалось любопытным) начать на любимом форуме РМС
Выйдет русский перевод Эндокринологии старения , вот любопытные зарисовки
Macimorelin - синтетический агонист Рецептора к грелину для тестов на секрецию СТГ, прирост оценивается при пероральном ( !) приеме.
Неужели мы простимся с инсулиновой гипогликемией как тестом ? По крайней мере в поисках дефицита ГР?

"The current study confirms and extends earlier reports showing that antibody blockade of ActRII [activin type II receptor] with bimagrumab in human participants leads to a marked loss in fat mass, an increase in lean mass, and improvement in a range of metabolic biomarkers," the team wrote. "These findings suggest that blockade of the activin receptor with bimagrumab could provide a novel pharmacologic approach for managing patients with type 2 diabetes with excess adiposity."

Metformin as a stand-alone or adjuvant therapy was associated with improvement in acne in patients with polycystic ovary syndrome (PCOS), researchers reported in a study published the American Journal of Clinical Dermatology.

The investigators conducted a systematic review and meta-analysis regarding the efficacy of metformin in treating patients with acne related to PCOS. The review included randomized controlled trials, nonrandomized controlled trials, and open-label studies of patients with PCOS who were treated with metformin. Standardized mean differences (SMDs) were calculated for acne scores and odds ratios (ORs) for the presence of acne, with 95% confidence intervals (CIs).

The analysis included 51 studies with a total of 2405 patients with PCOS. The researchers found that metformin as adjuvant therapy led to greater improvement of acne scores compared with the same therapy without metformin (SMD −0.256; 95% CI −0.439 to −0.074). Pooling pre-metformin and post-metformin treatment data showed a significant decrease in acne scores after metformin use (SMD −0.712; 95% CI −0.949 to −0.476). The presence of acne decreased significantly after metformin treatment (odds ratio [OR] 0.362; 95% CI 0.271-0.485).

Among several limitations, the included studies varied regarding grading acne severity or assessing the presence of acne, metformin dosage, and treatment duration. Also, the investigators could not account for confounding factors such as body mass index, glucose, insulin, and hormone status or assess medication adherence.

The researchers noted that further studies with standardized acne grading scales are needed to more precisely assess the effect of metformin on acne in women who have PCOS.

“Based on this systematic review and meta-analysis, metformin, either as individual or adjuvant therapy, may be effective in treating acne in women with PCOS, especially among those who have diabetes or wish to conceive,” stated the study authors.

“After considering other indications and contraindications, metformin can be considered for use in women with polycystic ovary syndrome for treatment of acne,” the study authors stated.

Reference

Yen H, Chang Y-T, Yee FJ, Huang Y-C. Metformin therapy for acne in patients with polycystic ovary syndrome: A systematic review and meta‑analysis [published online October 13, 2020]. Am J Clin Dermatol. doi: 10.1007/s40257-020-00565-5

This article originally appeared on Dermatology Advisor

Давно идёт вежливый, но ожесточённый спор: в чём причина СПКЯ? Андреа Дунайф ратует за инсулин, Джон Маршалл за частые пульсы ГнРГ, не подавляемые прогестероном. Его данные безупречно доказаны шаг за шагом. Но как ни крути, а ановуляция с образованием кист это частая черта ожирения. И то, что снижение инсулина восстанавливает овуляции и снижает андрогены это факт. И нужен кто-то умный, который придумает протокол ( или серию их) как сложить эти 2 и 2 вместе.

СПКЯ мы лечили кломифенoм, диетой, витаминами, адипозином ( мир его праху) и даже бийохинолом - и все равно кто- то беременел.
Боюсь, что СПКЯ разные.

A phase I study is now underway for an investigational, oral adrenocorticotropic hormone antagonist, CRN04894, aimed at the treatment of congenial adrenal hyperplasia and Cushing's disease, Crinetics Pharmaceuticals announced.

А вот это уже похуже:
Brain Tumor Risk Upped With Synthetic Progestogen
— Absolute risk still low, however, and product not currently approved in U.S.
by Kristen Monaco, Staff Writer, MedPage Today February 3, 2021


A box of cyproterone acetate tablets over a computer rendering of a brain tumor
Women taking the synthetic progestogen cyproterone acetate were at increased risk for brain tumors, a French study found.

The analysis of data on over 250,000 girls and women who filled a prescription for cyproterone acetate showed that these individuals had a six-fold higher risk for developing an intracranial meningiomas compared with women not using the hormone (adjusted hazard ratio 6.6, 95% CI 4.0-11.1), reported Alain Weill, MD, of EPI-PHARE Scientific Interest Group in France, and colleagues in The BMJ.

Cyproterone acetate, a synthetic progestogen with antiandrogen effects, is currently approved in most European countries but not in the U.S. Across Europe, the drug has varying indications, including for hirsutism or hyperandrogenism spectrum in women and inoperable prostate cancer and paraphilias in men. In addition, given the antiandrogen properties, cyproterone acetate is also used as feminizing hormone therapy for transgender women.

Weill and colleagues also found that the relationship was dose-dependent, with women exposed to a cumulative dose of more than 60 g of cyproterone acetate -- the highest exposure group -- showing a nearly 22-fold increased risk (aHR 21.7, 95% CI 10.8-43.5).

Although the absolute risk for intracranial meningiomas requiring surgery or radiotherapy was low, there were 69 cases of meningiomas reported in women exposed to the hormone (289,544 person-years of follow-up) compared with 20 cases in the control group not exposed (439,949 person-years of follow-up).

This increased risk rapidly dropped off after discontinuation of cyproterone acetate. After the hormone was stopped for 1 year, the risk for meningioma dropped to only 1.8-fold higher than women never exposed (aHR 1.8, 95% CI 1.0 to 3.2). However, the risk was still more than four times higher if the cumulative dose prior to discontinuation was 12 g or more (aHR 4.2, 95% CI 2.2-8.0).


These new meningioma cases specifically tied to cyproterone acetate tended to be located in the anterior skull base and middle skull base -- mostly in the medial third of the middle skull base involving the spheno-orbital region, the researchers noted. In particular, there was a 47-fold (95% CI 14.9 -149.1) increased risk for meningiomas in the anterior skull base tied to prolonged use of cyproterone acetate.

Nearly all were treated with a neurosurgical procedure, while few received radiotherapy alone.

"Most of the participants with meningioma had taken cyproterone acetate for off-label indications, and around 30% had even continued or resumed cyproterone acetate after treatment of the meningioma, which has been formally contraindicated since 2011," the team wrote.

The observational analysis included data from 253,777 girls and women ages 7 to 70 from SNDS, a French administrative healthcare database covering the entire population of the country. All had been recorded as having at least one reimbursement for cyproterone acetate between 2007 and 2014; the majority were prescribed the therapy by a gynecologist (57%), followed by a general practitioner (18%), dermatologist (12%), or endocrinologist (10%).


Similar findings were seen in a separate analysis looking only at transgender patients prescribed the agent. There was a high risk for meningioma among these patients, with an incidence rate of 20.7 cases per 100,000 person-years. Notably, these patients tended to receive much higher daily doses compared with other patient populations, with all cases of meningioma occurring in those taking daily doses of 100-150 mg, the researchers said.

"People who use high-dose cyproterone acetate for at least 3 to 5 years should be informed about the increased risk of intracranial meningioma," Weill's group wrote. "The indication of cyproterone acetate should be clearly defined and the lowest possible daily dose used."

However, if prolonged high-dose use is necessary, patients should be screened for meningioma via magnetic resonance imaging, the researchers advised.

"In patients with a documented meningioma, cyproterone acetate should be discontinued, because the meningioma might regress in response to treatment discontinuation and invasive treatment could be avoided," the team concluded.

SAN DIEGO, March 20, 2021 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced that it will present additional positive data from its Phase II CAHlibrate study of crinecerfont, an investigational, oral, non-steroidal corticotropin-releasing factor type 1 (CRF1) receptor antagonist for the potential treatment of classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD), at ENDO 2021, the Endocrine Society's annual meeting, on March 20–23, 2021. These new analyses, based on data from seven male subjects with classic CAH receiving crinecerfont, demonstrate dose-dependent decreases in androstenedione (A4), a key marker of CAH control and precursor to testosterone, with similar dose-dependent decreases in the A4 to testosterone ratio. Testosterone levels were preserved despite the marked reductions in A4, suggesting a positive effect on reproductive hormones and providing early indications of improved testicular function. During the ENDO 2021 Virtual Poster Hall, Neurocrine Biosciences will present the Phase II CAHlibrate data, along with two additional abstracts that highlight real-world data evaluating the impact of CAH in adult and pediatric patients.

Начинается эра синтетических модуляторов разных рецепторов.
Сомаверт был первой ласточкой: оба связывающих места гормона роста были модифицированы чисто по конформационным соображениям, одно место с усиленным связыванием с одним рецептором, другое с конформацией , не дающей ему связаться с другом рецептором. Как результат, получился антагонист гормона роста: нет димеризации рецепторов, - нет эффекта.
Компания Кринетикс уже сделала чистый агонист соматостатинового рецептора Тип 2: это маленькая молекула, структурально ничего общего с соматостатином не имеющая, чисто конформация связывающего места. Очень хорошо работает при акромегалии.
У них есть подобного же типа антагонист для 5 типа: для гипогликемии у детей и при инсулиномах
Есть у них и small molecule антагонист кортиколиберина, как и описанный выше Г.А.
Антагонисты гонадолиберина для преждевременного полового созревания, антагонисты ТТГ и ИФР-1 для офтальмопатии Грейвса на горизонте.
Громадный плюс такого подхода это то, что все они не разрушаются пептидазами ( они не пептиды) , и они эффективны пер ос.

То, что менингиомы растут на прогестероне, известно давно, и назначение агонистов прогестерона было крайне ограничено у людей с менингиомами. Мифепристон применяется при них широко. Так что сюрприз малый, но аргумент сильный.

Вот понять бы нейротрансмиттер аппетита, так в течение года будет антагонист.

Благодарить за всё это надо бывшего президента США Ричарда Никсона: он создал программу "Война Против Рака". Как результат её, начались широчайшие исследования в молекулярной биологии и смежных дисциплинах. Начали практически с нуля, но мы теперь чуть ли не каждые пару месяцев пожинаем плоды этой " войны" в виде новых и новых лекарств.
А Сан Диего это Кремниевая Долина всяческих " либеринов" и агонистов/антагонистов их. Там этих маленьких стартапов вагон. Уверен, что кто-то работает над не-пептидным антагонистом гормона роста.

Я прошу прощения у администрации форума- когда -то, на заре нашей работы, мы старательно переводили все наши новые сведения, сейчас, думаю,нет такой необходимости и, знаю, нет времени. И спасибо проф Баркану за очень важный комментарий

А вот потенциальный переворот в диагностике и локализации кортикотропином

doi: 10.1210/clinem/dgaa755

Группа из Индии создала радиомеченый CRH .100% идентификация кортикотропином, причем даже не видных на МРТ(!). Накладывание изображения ПЭТ на МРТ локализовало опухоли к правильному гемигипофизу. А эктопические кортикотропиномы давали отрицательный аптэйк в гипофизе.

Пока только 24 случая, так что нужен намного больший опыт с молекулой, но вангую, что это полностью заменит катетеризацию каменистых синусов, причем с лучшими результатами.

Я не упомню другой статьи в JCEM за последние годы, которая заставила бы меня встать и снять шляпу.
Я им написал поздравление, и они мне ответили, что это еще ничего: у них уже есть еще лучшая молекула:-)
Абсолютные молодцы!

For patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, oral tildacerfont for up to 12 weeks helped to normalize adrenocorticotropic hormone and androstenedione levels in two phase II studies. (Journal of Clinical Endocrinology & Metabolism)

Одна доза Макрелина ( масиморелин) продаётся за ... присядьте, пожалуйста.... $4,500 ( для полуобморочных словами: четыре тысячи пятьсот долларов. Американских).
Учитывая, что число больных с эпилепсией, аритмиями , стенокардией, которым надо исключать дефицит ГР можно сосчитать на пальцах одной, ешё не ампутированной, ноги, все остальные взрослые кандидаты на выявление этой "смертельной болезни" могут проходить инсулиновую гипогликемию или тест с глюкагоном, или аргинином. Макрелин не оценивает АКТГ/Кортизол. Детям надо делать ИТТ ( кроме эпилепсии, конечно, для них глюкагон или аргинин).

А вот вместо ИТТ для дефицита АКТГ хорошо бы попробовать мифепристон: намного проще, чем метопирон, не даёт тошноты, одна доза вечером (может быть ещё одна доза рано утром) и в 8-9 утра взять АКТГ и кортизол.
Кто-то хочет сделать работу?
Первым делом, конечно, у мужчин.

Дубль. Прошу пардону.

Мифипристон- гениально, надо попробовать.
Поговорю с производителями ( у меня Жанна не очень любит этот препарат, к сожалению)

Я его тоже не люблю. На мифепристоне невозможно следить за объективными лабораторными параметрами контроля Кушинга: они либо повышаются ( болезнь Кушинга), либо более-менее стоят на месте при всех остальных формах. Все решения принимаются на основании жалоб, что-то похожее на лечение антидепрессантами. Марк Молич мне плакался, что первые 3 месяца очень тяжелы для больного: качели от продолжения симптомов до надпочечниковой недостаточности ( причем кортизол при этом пробивает потолок, гипотония и пр.). А врачу надо отвечать на одно трагическое послание за другим, причем в громадном большинстве случаев все срочно, но заочно: телефонное решение полу-смертельных жалоб. Жалоба на тошноту: надпоч. недостаточность или семгу второй категории поел? Начинать дексаметазон 6-8 мг в день или рискнуть ?

Кетоконазол прост, дешев, надежен, и при этом заповедь Олбрайта «Измеряй что-то!» работает.
А вот как диагностический тест мифепристон может быть интересен. Для дефицита АКТГ уж точно, но можно попробовать его и при других « АКТГ/ кортизол» состояниях ( как насчет диф.диагноза энзиматических дефектов надпочечников? Если мне мой Альцхаймер не изменяет, здесь вроде говорили, что в РФ Синактена короткодействующего нет). Или диф. диагностика болезни Кушинга?

Назад к эндокринологии 30-40-х годов: есть какое-то соединение,- пробуй его при всех мыслимых и немыслимых болячках: Олбрайт так ввел эстрогены при акромегалии:-)

Эндокринология это такая большая и уютная песочница... играй в свое удовольствие.

The Journal of Clinical Endocrinology & Metabolism, 2021, Vol. 106, No. 9, 2600–2605
doi:10.1210/clinem/dgab373
Clinical Research Article
ISSN Print 0021-972X ISSN Online 1945-7197
Printed in USA 2600 [Ссылки могут видеть только зарегистрированные пользователи. ] © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.
For permissions, please e-mail: [Ссылки могут видеть только зарегистрированные пользователи. ]
Clinical Research Article
Three Cases of Subacute Thyroiditis Following
SARS-CoV-2 Vaccine: Postvaccination ASIA
Syndrome
Burçin Gönül İremli,1
Süleyman Nahit Şendur,1
and Uğur Ünlütürk1
1
Division of Endocrinology and Metabolism, Department of Internal Medicine, Hacettepe University
School of Medicine, Hacettepe, Ankara, Turkey
ORCiD number: 0000-0002-5054-1396 (U. Ünlütürk).
Received: 24 April 2021; Editorial Decision: 21 May 2021; First Published Online: 27 May 2021; Corrected and Typeset:
24 June 2021.
Abstract
Context: Autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome)
can be seen as a postvaccination phenomenon that occurs after exposure to adjuvants
in vaccines that increase the immune responses. There are very limited data regarding
ASIA syndrome following severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) vaccines.
Objectives: This work aims to report cases of subacute thyroiditis related to the SARSCoV-2 vaccine.
Methods: We describe the clinical, laboratory, and imaging features of 3 cases of
subacute thyroiditis after inactivated SARS-CoV-2 vaccine (CoronaVac®). Three female
healthcare workers have applied to our clinic with anterior neck pain and fatigue 4 to
7 days after SARS-CoV-2 vaccination. Two of them were in the breastfeeding period.
They were negative for thyroid antibodies, and there was no previous history of thyroid
disease, upper respiratory tract infection, or COVID-19. Laboratory test results and
imaging findings were consistent with subacute thyroiditis.
Results: SARS-CoV-2 vaccination can lead to subacute thyroiditis as a phenomenon of
ASIA syndrome. Subacute thyroiditis may develop within a few days after the SARSCoV-2 vaccination. Being in the postpartum period may be a facilitating factor for the
development of ASIA syndrome after the SARS-CoV-2 vaccination.
Conclusions: This is the first report of subacute thyroiditis as a phenomenon of ASIA
syndrome after inactivated COVID-19 vaccination. Clinicians should be aware that
subacute thyroiditis may develop as a manifestation of ASIA syndrome after the inactive

А вот уже природа играет в нашей песочнице - если был подострый на ковиде, логично, что он есть и на вакцину.

Oncology/Hematology
>
Renal Cell Carcinoma
FDA Approves First Drug for Von Hippel-Lindau-Associated Tumors
— Objective response or stable disease in 100% of renal cell carcinomas
by Charles Bankhead, Senior Editor, MedPage Today August 13, 2021

FDA APPROVED belzutifan (Welireg) over a computer rendering of renal carcinoma and an MRI of a hemangioblastoma
The FDA has approved the first therapy for cancers associated with von Hippel-Lindau (VHL) disease.

Belzutifan (Welireg), distributed by Merck, targets hypoxia-inducible factor 2α, which drives growth of malignant and benign tumors in VHL. In the absence of approved systemic therapies, most patients with VHL undergo multiple surgeries in their lifetime to remove renal cell carcinoma (RCC) and other VHL-associated tumors. The approval encompasses VHL-associated RCC, central nervous system (CNS) hemangioblastomas, and pancreatic neuroendocrine tumors not requiring immediate surgery.


Supporting data for the approval included results of a phase II trial of single-agent oral belzutifan in 61 patients with VHL-associated RCC, all of whom had non-RCC tumors as well. Eligible patients had at least one measurable RCC tumor, no prior systemic therapy for cancer, and no evidence of metastatic disease.

Patients received belzutifan once daily, continued until disease progression. The primary endpoint was objective response rate (ORR) in VHL-associated RCC. Secondary endpoints included ORR in non-RCC neoplasms, duration of response in RCC and non-RCC tumors, and safety.

As initially reported at the 2021 virtual meeting of the American Society of Clinical Oncology (ASCO), all 61 patients had some type of pancreatic neoplasm (pancreatic neuroendocrine tumors in 36% of cases), 50 (82%) had CNS hemangioblastomas, and 16 (26%) had retinal lesions.

The results showed that 30 of 61 (49%) patients achieved partial responses in RCC lesions with belzutifan. An additional 30 patients had stable disease, including four who had unconfirmed partial responses. The remaining patient was not evaluable for response, meaning that no patient in the intention-to-treat analysis had progressive disease during treatment with belzutifan. The median time to treatment response was 8.2 months, and median duration of response had yet to be reached.


In the patients with non-RCC tumors, the ORR was 77% in pancreatic lesions (including six complete responses), 90% (20 of 22) in pancreatic neuroendocrine tumors (three complete responses), and 30% (15 of 50) in CNS hemangioblastomas (three complete responses). Two CNS lesions progressed, but no patient had progression of pancreatic or pancreatic neuroendocrine tumors.

The most common adverse event (AE) associated with belzutifan treatment was anemia (90.2% of patients), which is considered an on-target effect of the drug, explained Ramaprasad Srinivasan, MD, of the National Cancer Institute, during an ASCO poster presentation. Other common AEs included fatigue (65.6%), headache (41.0%), dizziness (39.3%), nausea (34.4%), and dyspnea (23.0%). No patients had a grade 4 AE, and the most frequent grade 3 AEs were anemia (8.2%), hypertension (8.2%), and fatigue (4.9%).

An oral peptide drug with the same amino acid sequence as injectable teriparatide (Forteo) significantly boosted bone mineral density (BMD) in postmenopausal woman at risk for osteoporosis, a researcher reported from a dose-ranging phase II trial.

Six months of treatment with the oral agent, called EBP05, at doses of 2.5 mg/day led to a mean 2.5% increase in lumbar spine BMD versus a slight decrease in women receiving placebo (P<0.002), said Arthur Santora, MD, PhD, of Entera Bio's U.S. office in Boston. (The company, which is developing EBP05, is headquartered in Jerusalem.)

The FDA granted accelerated approval to the first drug to spur growth in kids with the most common form of dwarfism, the agency announced on Friday.

Vosoritide (Voxzogo), a once-daily injectable treatment, is indicated for children 5 years and older with achondroplasia and who still have open growth plates -- in other words, these children still have the potential to grow.
Дай Бог!

Увы, метформин не антиканцероген при раке молочной железы
 

SAN ANTONIO -- Metformin did not improve outcomes in patients with early breast cancer, regardless of estrogen receptor (ER) or progesterone receptor (PR) status, according to results from the phase III CCTGMA.32 trial.

However, an exploratory analysis suggested that metformin may have a beneficial effect in HER2-positive breast cancer, said Pamela J. Goodwin, MD, MSc, of Mount Sinai Hospital/Lunenfeld-Tanenbaum Research Institute at the University of Toronto, during a presentation at the San Antonio Breast Cancer Symposium.

Of the 620 patients with HER2-positive breast cancer analyzed, invasive disease-free survival (IDFS) was improved in those who received metformin (HR 0.64, 95% CI 0.43-0.95, P=0.03), as was overall survival (OS; HR 0.53, 95% CI 0.30-0.98, P=0.04).

Goodwin explained that this exploratory analysis was informed by the results of the METTEN study, in which the pathologic complete response rate more than doubled when neoadjuvant metformin was added to anthracycline/taxane-based chemotherapy and trastuzumab in HER2-positive patients who had at least one C allele of a prespecified ATM-associated single-nucleotide polymorphism (SNP).

"The presence of any C allele of this SNP is associated with metformin benefit in diabetes," she pointed out.

"Importantly, there was a significant interaction by SNP (P=0.05) on the effect of metformin on IDFS, with those with any C allele having a hazard ratio of 0.51 (95% CI 0.31-0.83, P=0.0067)," the researchers reported. "Whereas those with the AA genotype had no evidence of a benefit with metformin (HR 1.32, 95% CI 0.58-2.96, P=0.51)."

A similar interaction was seen for OS. The 601 patients with any C allele had a reduction in death (HR 0.35, 95% CI 0.17-0.73, P=0.003), while those with the AA genotype showed no evidence of a metformin benefit (HR 2.15, 95% CI 0.56-8.36, P=0.26).

The randomized, placebo-controlled CCTGMA.32 trial enrolled 3,649 patients ages 18 to 74 with T1-3 N0-3 M0 breast cancer and no evidence of distant metastases from 2010 to 2013. All patients were treated with standard therapy and were randomized to receive metformin 850 mg twice daily for 5 years or placebo.

In 2016, futility was declared in ER/PR-negative patients and the intervention was stopped in that group, with blinding and follow-up continuing. Thus, the study's primary analysis focused on the 2,533 ER/PR-positive patients (mean age 52.7, mean BMI 28.8).

At a median follow-up of 96.2 months, 234 IDFS events occurred in the metformin arm versus 321 in the placebo arm, 75.6% of which were due to breast cancer (HR 1.01, 95% CI 0.84-1.21, P=0.92). There were 131 deaths in the metformin arm and 119 in the placebo arm, with 75.8% of deaths related to breast cancer (HR 1.10, 95% CI 0.86-1.41, P=0.47).

Similar results for other breast cancer outcomes were observed, including distant disease-free survival (HR 0.99, 95% CI 0.80-1.23, P=0.94) and breast cancer-free interval (HR 0.98, 95% CI 0.80-1.20, P=0.87).

In a follow-up to the futility results in the 1,116 patients with ER/PR-negative breast cancer at a median follow-up of 96 months, there was no benefit seen with metformin for either IDFS (HR 1.01, 95% CI 0.79-1.30, P=0.92) or OS (HR 0.89, 95% CI 0.64-1.23, P=0.46).

"Subjects with HER2-positive breast cancer -- notably those with at least one C allele of the ATM-associated rs11212617 SNP -- experienced improved IDFS and overall survival with metformin," Goodwin concluded. "However, no P value 'spend' was allocated to this comparison. As a result, it requires replication in a prospective trial focusing on the HER2-positive population."

WALTHAM, Mass., Dec. 20, 2021 (GLOBE NEWSWIRE) -- Viridian Therapeutics, Inc. (NASDAQ: VRDN), a biotechnology company advancing new treatments for patients suffering from serious diseases underserved by current therapies, today announced the first subject was dosed in a Phase 1/2 proof-of-concept clinical trial for VRDN-001, a monoclonal antibody that blocks the IGF-1 receptor with sub-nanomolar potency. IGF-1R blockade is a clinically validated mechanism of action for the treatment of TED.

The Phase 1/2 trial is designed to evaluate safety, tolerability, pharmacokinetics, and potential efficacy of VRDN-001. The trial includes both healthy volunteers and randomized, placebo-controlled cohorts of TED patients and will assess multiple measures of the signs and symptoms of TED, including proptosis – the bulging of eyes characteristic of TED. The Company expects to announce top line data from the proof-of-concept portion of the trial in the second quarter of 2022. The trial protocol allows for additional TED patient cohorts to assess differing treatment paradigms that may offer advantages over currently available therapies and may reduce the burden of patient treatment.

“We are excited to initiate our first clinical trial of VRDN-001. This trial is designed to quickly assess the potential of VRDN-001 to offer a new option for patients suffering from TED, and to inform how we can optimize VRDN-001 development to best meet patients’ needs,” stated Jonathan Violin, Ph.D., Viridian Therapeutics’ President and CEO. “VRDN-001 exemplifies Viridian’s patient-centric model of innovation that leverages proven biology and technology to efficiently craft medicines to meet the needs of patients and healthcare providers.”

TED - это синдром хронической усталости?

НЕт , это Thyrоid Eye Disease - так даже назывался журнал для больных , когда -то я написала там заметку и долго получала журнал, поэтому мне не пришла в голову мысль о расшифровке.

Middle-age and older men with lower total testosterone didn't see any increased risk for myocardial infarction (MI), stroke, heart failure, or major adverse cardiovascular events. However, those with lower sex hormone-binding globulin levels did see a higher risk for MI. (Annals of Internal Medicine)


Saniona announced it initiated a phase IIb clinical trial of Tesomet -- an investigational fixed-dose combination therapy of the triple monoamine reuptake inhibitor tesofensine and the beta-1 selective blocker metoprolol -- for the treatment of Prader-Willi syndrome. The treatment is also being tested for hypothalamic obesity in another phase IIb trial.

Estrogen and Progesterone Therapy and Meningiomas Get access Arrow
Mirella Hage, Oana Plesa, Isabelle Lemaire, Marie Laure Raffin Sanson
Endocrinology, Volume 163, Issue 2, February 2022, bqab259, [Ссылки могут видеть только зарегистрированные пользователи. ]
Published: 22 December 2021 Article history
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Abstract
Meningiomas are common intracranial tumors with a female predominance. Their etiology is still poorly documented. The role of sexual hormones has long been evoked, and data have been conflicting across studies. However, a dose-dependent relationship between the incidence and growth of meningiomas and hormonal treatment with the progestin cyproterone acetate (CPA) has recently been established. CPA-associated meningiomas seem to be mainly located in the anterior and middle skull base, are more likely to be multiple, may harbor P1K3CA mutations in up to one-third of cases, and are more common with a longer duration of treatment. A similar but lower risk of meningiomas has been recently reported with the use of chlormadinone acetate and nomegestrol acetate as progestin treatments. Concerning hormonal replacement therapy (HRT) in menopausal patients, evidence from epidemiological studies seem to favor an increased risk of meningiomas in treated patients although a recent study failed to show an increased growth of meningiomas in HRT treated vs nontreated patients. Until larger studies are available, it seems wise to recommend avoiding HRT in patients with meningiomas. Evidence from published data does not seem to support an increased risk of meningiomas with oral contraceptive oral contraceptive (OR) use. Data are too scarce to conclude on fertility treatments. Based on studies demonstrating the expression of hormonal receptors in meningiomas, therapies targeting these receptors have been tried but have failed to show an overall favorable clinical outcome in meningioma treatment.

Как-то некомфортно

Viridian Therapeutics announced that the FDA cleared its investigational new drug application for VRDN-002, a next-generation IGF-1R antibody for the treatment of thyroid eye disease, to initiate a first-in-human phase I clinical trial.

Switching between generic levothyroxine products won't make much of a clinical difference, a new study suggested.

In a comparative effectiveness research study of 15,829 patients, those who switched up their generic levothyroxine product didn't see any change in serum thyrotropin (TSH) levels compared with those who continued taking the same product, Juan Brito, MD, MSc, of the Mayo Clinic in Rochester, Minnesota, and colleagues reported.

Comparing lab results 6 weeks to 12 months after the index date, the proportion with normal TSH levels (0.3-4.4 mIU/L) was no different between the group who switched their levothyroxine product and so-called non-switchers (84.5% vs 82.7%; P=0.07), according to the findings in JAMA Internal Medicine.


Similarly, 3.1% of non-switchers had markedly abnormal TSH levels (<0.1 mIU/L or >10 mIU/L) versus 2.5% of switchers (P=0.14). And there were also no between-group differences in the proportion with abnormal TSH levels. Overall, average TSH levels were the same, at 2.7 mIU/L for both groups.

"Generic levothyroxine preparations are less expensive and have been rated by the FDA as bioequivalent to their brand name reference-listed drugs," Brito's group explained. "However, generic levothyroxine has been less widely prescribed than other generic pharmaceutical products."

"One potential reason for this may be the lingering concerns about an association between switching levothyroxine products sourced from different manufacturers and the stability of thyroid hormone levels," they continued.

"When clinicians prescribe a particular brand name product (indicating dispense as written), that specific product is dispensed to a patient for the duration of the prescription," the researchers pointed out. "In contrast, when clinicians prescribe generic levothyroxine, pharmacists can substitute a variety of generic levothyroxine preparations made by different manufacturers (e.g., Mylan, Sandoz, or Lannett) without requiring clinician notification or approval."

And this sparked concerns in the field, they noted, to the degree that the American Thyroid Association's 2014 clinical guidelines specifically recommended against levothyroxine switching from different manufacturers due to concerns of bioequivalence.

"Given these concerns, it is important to understand the implications of switching among different generic levothyroxine products for TSH levels," Brito's group wrote, explaining the impetus for the study.

For their analysis, the researchers drew upon data from deidentified administrative claims linked to lab results from commercially insured adults and Medicare Advantage enrollees. All patients included had filled a generic levothyroxine preparations from the top three most common manufacturers -- Mylan, Sandoz, and Lannett -- from 2008 to 2019. This included both new and prevalent users.

Roughly three-fourths of the study population were women, and the average age was 59. Over half of the cohort were receiving a daily levothyroxine dose of 50 μg or less. Exclusion criteria included pregnancy, hypopituitarism, hyperthyroidism, or any medical condition that can affect TSH levels.

During the analysis, 13,049 patients (82.4%) continued taking the same sourced preparation, while 2,780 patients (17.6%) switched between generic levothyroxine preparations. Using 1:1 propensity matching, the group compared 2,780 patient pairs to measure the implications of switching products.

Acknowledging that these findings conflict with current clinical practice guidelines, Brito's group said this should only reassure both patients and clinicians that switching among products is unlikely to bear any substantial impact.

They also suggested that these findings may help "curtail the relative underuse of generic levothyroxine in the U.S. because one of the main concerns of prescribing generic levothyroxine is the lack of control over switching among different generic products."

They noted that between 2007 to 2016, roughly three-fourths of thyroid hormone prescriptions were for generic levothyroxine versus 97% of other drugs that had both brand-name and generic options available.

"The underuse of generic levothyroxine has considerable financial implications for patients and health care systems," the group underscored.

One limitation to the study was the lack of a comparison group that specifically measured switching from brand-name levothyroxine products to generics.

НО лучше все же попусту не менять

Я с крайней осторожностью бы экстраполировала результаты исследования брендовых дженериков на продукты российского фармпроизводства...

Adding recombinant human (rh) insulin to human milk and formula helped preterm infants reach full enteral feeding faster, the randomized FIT-04 study found.

Among 303 infants with a gestational age of 26 to 32 weeks, those receiving either low-dose rh insulin (400 μIU/mL milk) or high-dose rh insulin (2,000 μIU/mL milk) for 28 days were able to achieve an enteral intake of ≥150 mL/kg per day for 3 consecutive days more quickly than infants on placebo, reported Johannes B. van Goudoever, MD, PhD, of Amsterdam University Medical Centers in the Netherlands, and colleagues in JAMA Pediatrics.
Как Вам?

Во-первых, инсулин сам по себе легкоусваиваемый белок :) а во-вторых, так анаболическое же действие у инсулина... а учитывая повышенную проницаемость кишечника у новорожденных, особенно недоношенных, и несовершенство ферментных систем, вполне возможно, что микроколичества доходят в кровоток "непереваренными" и малость стимулируют все, что только могут...

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.

Adverse events (AEs) that occurred more often with baricitinib than with placebo were acne, elevated creatinine kinase levels, and increased LDL and HDL cholesterol, King said in a presentation at the American Academy of Dermatology (AAD) meeting.

The 52-week results showed continued improvement as compared with results after 36 weeks of follow-up, which were reported simultaneously in the New England Journal of Medicine.

"Continued treatment with baricitinib after 36 weeks resulted in further increases in the proportion of patients who achieved scalp, eyebrow, and eyelash hair regrowth," said King. "The proportion of patients achieving a SALT score <20 and/or a SALT score <10 -- and that's kind of a high bar -- continued to increase. The proportion of patients achieving ClinRO [Clinician Reported Outcome] for eyebrow and eyelash hair loss ... also continued to increase, restoring to nearly normal or normal."

"This is truly transformational for patients," he added. "These patients start out looking nothing like themselves, and they finish study, at least when it works, looking like themselves again, restored to normal."

Limited Treatment Options

An autoimmune condition with no approved therapies, alopecia areata affects men and women alike and causes rapid hair loss in the scalp, eyebrows, and eyelashes. The pathogenesis of the condition involves genetic and immune factors. Cytokines implicated in alopecia areata depend on the JAK pathway for intracellular signaling, providing a rationale for evaluating the therapeutic potential of JAK inhibition.

King reported findings from 52 weeks of follow-up in the BRAVE-AA1 and BRAVE-AA2 randomized, placebo-controlled evaluations of baricitinib in adults with active alopecia areata associated with a SALT score ≥50 (at least 50% hair loss). Investigators at 169 centers in 10 countries randomized 1,200 patients 2:2:3 to placebo, baricitinib 2 mg, or baricitinib 4 mg.

The primary endpoint was the proportion of patients achieving a SALT score ≤20 at 36 weeks. Secondary endpoints included a SALT score ≤10 and a ClinRO of 0 or 1 (full eyebrow/eyelash coverage or minimal gaps) with at least a 2-point improvement from baseline. The 52-week assessment focused on the same three outcomes. Patients allocated to the JAK inhibitor remained in their assigned dose groups, and placebo-treated patients with SALT score >20 switched to baricitinib after 36 weeks.

The study population had a median age of about 37, and women accounted for about 60% of all patients. About two-thirds of the patients had an alopecia duration of <4 years, and >40% had alopecia universalis. Baseline SALT score averaged about 85 across the placebo and baricitinib groups.

Key Results

The 36-week results showed that 34% of patients in the baricitinib 4-mg arm had a SALT score ≤20, as compared with 19.7% of the 2-mg arm, and 4.1% of the placebo group. At 52 weeks, the proportion of patients with SALT score ≤20 had increased to 39% with the 4-mg baricitinib dose and 22.6% with the lower dose.

For the more stringent SALT score ≤10, response rates at 36 weeks were 24.9%, 11.8%, and 2.3%, respectively for baricitinib 4 mg, baricitinib 2 mg, and placebo. Rates increased to 28.9% and 15.3% for the baricitinib arms at 52 weeks.

Rates of ClinRO response for eyebrows increased from 33.0% at 36 weeks to 44.1% at 52 weeks with the higher dose of baricitinib and from 15.8% to 22.9% with the 2-mg dose. In the placebo group, 3.8% of patients met ClinRO response criteria at 36 weeks.

Changes in ClinRO response for eyelashes from 36 to 52 weeks were 33.6% to 45.3% with baricitinib 4 mg and from 12.0% to 25.5% with baricitinib 2 mg. The placebo group had a 4.3% ClinRO response at 36 weeks.

In response to a question from the audience, King said patients with longstanding alopecia areata are not good candidates for treatment with the JAK inhibitor. A patient with a 10-year history of the hair loss is unlikely to benefit, although outliers do exist.

Similar results emerged from a subgroup analysis of phase IIb/III placebo-controlled study of a different JAK inhibitor. An analysis of 105 adolescents (mean age 15) included in the overall study population showed that the JAK3/TEC inhibitor ritlecitinib led to SALT score ≤20 responses in 17%-28% of patients treated for 24 weeks with one of five doses of the drug. Additionally, 17%-28% of patients met criteria for SALT ≤10 responses.

From 22%-61% of patients treated with ritlecitinib rated results as improved or much improved on Patient Global Impression of Change index. The best results occurred in patients randomized to a 200-mg loading dose of the drug followed by 50 or 30 mg daily, reported Maria Hordinsky, MD, of the University of Minnesota in Minneapolis, and colleagues, in an AAD poster presentation. The most common AEs (including the placebo group) were headache, nasopharyngitis, and upper respiratory infection.

The FDA has approved a new oral testosterone undecanoate capsule (Tlando) for hypogonadism, Antares Pharma announced.

This androgen is indicated for testosterone replacement therapy in adult men for conditions associated with a deficiency or absence of endogenous testosterone, including congenital or acquired primary hypogonadism, as well as congenital or acquired hypogonadotropic hypogonadism.

"The FDA approval of Tlando brings to market an oral formulation of testosterone that we believe will prove beneficial to physicians and their patients," said Robert F. Apple, president and CEO of Antares Pharma.

The approval was based on a phase III trial in which about 80% of participants achieved 24-hour average serum testosterone concentrations within the normal range between 300 to 1,080 ng/dL with Tlando, meeting the primary efficacy endpoint.

Prior to treatment initiation, diagnosis of hypogonadism must be confirmed via morning measurements of serum testosterone concentrations on at least two separate days to see if levels are below the normal range.

The recommended dosage is 225 mg orally twice daily with food. It does not require dose titration.

"We believe Tlando's oral formulation and convenient dosing, which requires no titration, differentiates it from other treatment options," noted Apple.

The drug was also deemed a Schedule III controlled substance, due to risks of abuse and misuse of testosterone.

Отлично. Давно не хватало хорошего перорального тестостерона. Хотя посмотрим еще, сколько будет стоить...

BOSTON -- About half of patients with longstanding vitiligo obtained significant repigmentation that persisted for at least a year with the topical Janus kinase (JAK) inhibitor ruxolitinib (Opzelura), two randomized trials showed.

In one trial, 52.6% of patients randomized to ruxolitinib cream had at least 75% improvement in the Facial Vitiligo Area Scoring Index (F-VASI75) at 52 weeks. In the second trial, 48% of patients met F-VASI75 response criteria at 52 weeks. Patients in the trials who switched from placebo to ruxolitinib after 24 weeks also had substantial improvement at 52 weeks.

The most common treatment-related adverse events (TRAEs) with ruxolitinib were application-site acne and pruritus, reported David Rosmarin, MD, of Tufts Medical Center in Boston, during the American Academy of Dermatology (AAD) meeting here.

"Half of patients who applied ruxolitinib cream from day 1 achieved F-VASI75 and T-VASI50 [trunk] responses by week 52," said Rosmarin. "Efficacy at week 52 in crossover patients, after 28 weeks of ruxolitinib cream, was consistent with week-24 data in patients who applied ruxolitinib cream from day 1. Ruxolitinib cream was well tolerated, and no serious treatment-related adverse events were reported."

Also at AAD, preliminary data from a trial of oral JAK inhibitor ritlecitinib, presented by Yuji Yamaguchi, MD, PhD, of Pfizer, provided evidence that the drug halted progression of active vitiligo lesions and induced repigmentation in stable lesions, with consistent results for up to 48 weeks across the range of Fitzpatrick skin types.

Long-Term Ruxolitinib Outcomes

Rosmarin previously reported the primary outcome for the TRuE-V1 and TRuE-V2 trials, which showed that ruxolitinib 1.5% cream BID significantly increased the F-VASI75 response rate at 24 weeks versus vehicle. The updated report included ruxolitinib-treated patients who continued the JAK inhibitor to week 52, as well as placebo-treated patients who switched to ruxolitinib after completing the 24-week randomized trial.

Ожидаемый прорыв

Men taking metformin were more likely to have offspring with birth defects, a Danish study found.

Newborns with fathers who took metformin during the development of fertilizing sperm had a 40% higher frequency of birth defects compared with newborns whose fathers used insulin (adjusted OR 1.40, 95% CI 1.08-1.82), reported Maarten J. Wensink, MD, PhD, of the University of Southern Denmark, and colleagues.

The same did not hold true for offspring with fathers who took sulfonylureas versus insulin (aOR 1.34, 95% CI 0.94-1.92), they pointed out in the Annals of Internal Medicine.

Неприятно... Мб, что-то не так посчитали?

Как-то с трудом верится. А поправки на длительность диабета, метаболический синдром, прием препаратов от АГ, наличие осложнений?.. надо будет вчитаться в трайл.

это не трайл, а ретро-наблюдение [Ссылки могут видеть только зарегистрированные пользователи. ]

простой пример, как выводы зависят от статистики:

и на метформине и на сульф-мочевине был прирост на 35-40%, по сравнению с инсулином, НО на метФ было в 2 раза больше пациентов, поэтому 40% прирост оказался стат. состоверным, на на СуМо 34% повышение - нет, лишь потому, что метф прописывали в 2 раза чаще: Metformin-exposed offspring (n = 1451) had an elevated birth defect frequency (aOR, 1.40 [CI, 1.08 to 1.82]). For sulfonylurea-exposed offspring (n = 647), the aOR was 1.34 (CI, 0.94 to 1.92).

прямо скажем, что из-за редкости назначения сульфМ она статистически не дотянула до 1/3 избыточных врожденных проблем, а метформин - оказался инфант-террибль

очень хочется думать так.

Targeting 11-Beta Hydroxylase With [131I]IMAZA: A Novel Approach for the Treatment of Advanced Adrenocortical Carcinoma Get access Arrow
Stefanie Hahner, Philipp E Hartrampf, Patrick W Mihatsch, Marc Nauerz, Britta Heinze, Heribert Hänscheid, Carmina Teresa Fuß, Rudolf A Werner, Christina Pamporaki, Matthias Kroiss ... Show more
The Journal of Clinical Endocrinology & Metabolism, Volume 107, Issue 4, April 2022, Pages e1348–e1355, [Ссылки могут видеть только зарегистрированные пользователи. ]

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited treatment options. Theranostic approaches with adrenal specific radiotracers hold promise for improved diagnostics and treatment.

Objective
Here, we report a new theranostic approach to advanced ACC applying (R)-1-[1-(4-[123I]iodophenyl)ethyl]-1H-imidazole-5-carboxylic acid azetidinyl amide ([123I]IMAZA) for diagnostic imaging and [131I]IMAZA for radionuclide therapy.

Methods
Sixty-nine patients with nonresectable, metastatic ACCs were screened using a diagnostic [123I]IMAZA scan. Patients with significant uptake in all tumoral lesions were offered treatment with [131I]IMAZA. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1), and adverse effects were assessed by Common Toxicity Criteria (version 5.0).

Results
After screening, 13 patients were treated with a median of 25.7 GBq [131I]IMAZA (range 18.1-30.7 GBq). Five individuals received a second treatment course. Best response was a decrease in the RECIST target lesions of –26% in 2 patients. Five patients with disease stabilization experienced a median progression-free survival of 14.3 months (range 8.3-21.9). Median overall survival in all patients was 14.1 months (4.0-56.5) after therapy. Treatment was well tolerated, in other words no severe toxicities (CTCAE grade ≥3) were observed.

Conclusion
In patients with advanced ACC refractory to standard therapeutic regimens, [131I]IMAZA treatment was associated with disease stabilization and nonsignificant tumor size reduction in a significant patient fraction and only limited toxicities. High [131I]IMAZA-uptake in tumor lesions was observed in 38.5% of patients with advanced ACC, rendering [131I] IMAZA a potential treatment option in a limited, well-defined patient fraction. Further clinical trials will be necessary to evaluate the full potential of this novel theranostic approach.

Как-то напряжно...Ther Clin Risk Manag. 2020; 16: 245–259.
Published online 2020 Apr 8. doi: 10.2147/TCRM.S243462
PMCID: PMC7152545
PMID: 32308402
Hypophosphatemia Associated with Intravenous Iron Therapies for Iron Deficiency Anemia: A Systematic Literature Review
John A Glaspy,1 Michelle Z Lim-Watson,2 Michael A Libre,3 Swagata S Karkare,3 Nandini Hadker,3 Aleksandra Bajic-Lucas,2 William E Strauss,2 and Naomi V Dahl2
Author information Article notes Copyright and License information

Iron deficiency anemia (IDA) is a prevalent yet underdiagnosed condition with a significant impact on quality of life. Oral iron supplementation is often poorly tolerated or yields inadequate response, requiring the use of intravenous iron (IVI) in some patients. Administration of certain IVI preparations has been associated with decreases in serum phosphate levels and clinically significant hypophosphatemia, which has been reported to lead to adverse events including serious fatigue and osteomalacia.

Objective
The purpose of this study was to systematically assess the prevalence, clinical consequences, and reporting of treatment-emergent hypophosphatemia within literature investigating IVI therapies marketed in the United States (US).

Methods
A systematic literature review (SLR) was conducted using the PubMed database to identify publications reporting serum phosphate levels or rates of hypophosphatemia within adult IDA patient populations receiving current US-marketed IVIs.

Results
The SLR yielded 511 unique publications, with 40 records meeting the final inclusion criteria. Most studies did not report phosphate monitoring methodology or an explicit definition of hypophosphatemia. Hypophosphatemia rates ranged from 0.0% to 92.1% for ferric carboxymaltose (FCM), 0.0% to 40.0% for iron sucrose, 0.4% for ferumoxytol, and 0.0% for low-molecular-weight (LMW) iron dextran. Randomized controlled studies described hypophosphatemia as “asymptomatic” or did not report on other associated sequelae. Eleven case reports detailed treatment-emergent hypophosphatemia in patients treated with FCM. Patients with acute hypophosphatemia primarily developed severe fatigue; those with repeated FCM dosing developed chronic hypophosphatemia associated with osteomalacia and bone deformities.

Conclusion
Studies analyzed in this SLR reported a range of hypophosphatemia rates, with the highest consistently seen in patients treated with FCM. Across the clinical literature, there appeared to be minimal standardization of phosphate monitoring and definitions of hypophosphatemia. Although multiple cases have documented serious clinical consequences of hypophosphatemia associated with certain IVIs, current trials neither consistently nor adequately assess the frequency and severity of treatment-emergent hypophosphatemia and may underestimate its prevalence.

По большому счету не очень напрягает, главное, помнить об этом, отслеживать и при необходимости корректировать.
Конечно, в России сейчас чаще применяют внутривенное введение железа, но все равно это ничтожно мало, особенно вдали от "центров цивилизации", коими являются Москва и Питер.

Примерно так же ответил и наш гематолог , доктор Шкляев Большое спасибо за интересную статью о том, что терапия внутривенным Карбоксимальтозатом Железа может вызывать тяжелую гипофосфатемию и даже иногда остеомаляции!

Пока с такими проблемами мы не сталкивались, но хорошо знаем о том, что снижение уровня фосфора является наиболее частым побочным эффектом (в инструкции к препарату (Феринжект) это чётко прописано).

На мой взгляд основная причина того, что пока нам не доводилось сталкиваться с развитием выраженной гипофосфатемии и тем более остеомаляциями заключается в используемой нами дозе этого препарата внутривенного железа. В присланной Вами статье в США используют дозу 750 мг в/в 1 раз в неделю (N2). Мы же назначаем этот препарат по 100 мг/сутки (в/в капельно в 100 мл физ. р-ра очень медленно!) и за неделю, таким образом, набираем 500 мг. Далее обязательный перерыв на выходные дни и, если есть необходимость далее продолжаем проводить ещё 5 инфузий железа, т.о. чтобы доза достигла суммарно 1000 мг (за 12 дней).

В любом случае следует по возможности мониторировать уровень фосфора в сыворотке крови хотя бы после каждых 2-3 инфузий.

немного по диагностике этого осложнения:
In symptomatic patients a test panel including ionized calcium, total and bone-specific alkaline phosphatase, PTH, 25 (OH) vitamin D and 1,25 (OH)2 vitamin D is recommended. Typical findings in patients with intravenous iron-induced hypophosphatemia include mild hypocalcemia, normal or mildly reduced 25 (OH) vitamin D and markedly reduced 1,25 (OH)2 vitamin D with hyperparathyroidism and elevated total and bone-specific alkaline phosphatase. These changes can persist beyond the resolution of hypophosphatemia...

по ведению-профилактике:
Delay further intravenous iron doses and switch to iron formulations with lower hypophosphatemia risk in patients with hypophosphatemia.
It is unknown if vitamin D supplementation before FCM administration reduces hypophosphatemia and fracture risk.
...treatment was started in the majority of patients including oral (n = 36) or intravenous (n = 20) phosphate, activated vitamin D (n = 21),vitamin D (n = 9) or calcium (n = 10). Treatment outcome was highly variable and inconsistently reported. Considering the underlying pathogenesis driven by elevated intact FGF23, phosphate supplementation would not sustainably correct hypophosphatemia, but increase urinary phosphate excretion [[39], [40], [41]]. As clinical and biochemical changes apparently persist up to several months after the last FCM infusion, rational treatment approaches would include mitigation of secondary hyperparathyroidism with activated vitamin D, which was successfully used in some patients [40,42,43].
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Hypophosphatemia after intravenous iron therapy: Comprehensive review of clinical findings and recommendations for management. 2022
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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.

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.

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....

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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.

А можно и мне поучаствовать? 28 апреля 2022 г. - новое руководство ESMO по применению системной терапии при тяжелых случаях рака щитовидной железы [Ссылки могут видеть только зарегистрированные пользователи. ]
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.