Новости эндокринологии, записная книжка

[ghrh44]

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.

[Melnichenko]

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 доступны только зарегистрированным пользователям ] © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.
For permissions, please e-mail: [Ссылки доступны только зарегистрированным пользователям ]
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.

[Melnichenko]

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%).

[Dr.Vad]

это не трайл, а ретро-наблюдение [Ссылки доступны только зарегистрированным пользователям ]

[Dr.Vad]

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

[Melnichenko]

очень хочется думать так.

[Melnichenko]

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 доступны только зарегистрированным пользователям ]

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.

[Melnichenko]

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.

[FilippovaYulia]

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.

[ELENA_VLAD]

[Ссылки доступны только зарегистрированным пользователям ]
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.

[ELENA_VLAD]

[Ссылки доступны только зарегистрированным пользователям ]

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.

[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.