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%).

[Melnichenko]

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.)

[Melnichenko]

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!

[Melnichenko]

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."

[Melnichenko]

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.”

[FilippovaYulia]

TED - это синдром хронической усталости?

[Melnichenko]

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.

[Melnichenko]

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.

[Melnichenko]

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 доступны только зарегистрированным пользователям ]
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

[Melnichenko]

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.

[Melnichenko]

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

[FilippovaYulia]

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

[Melnichenko]

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.
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