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TouchREVIEWS in Endocrinology Apr 2024Osilodrostat is a novel potent oral steroidogenesis inhibitor with a non-steroidal chemical structure, recently approved for the treatment of adult patients with... (Review)
Review
Osilodrostat is a novel potent oral steroidogenesis inhibitor with a non-steroidal chemical structure, recently approved for the treatment of adult patients with endogenous Cushing's syndrome, and Cushing's disease not cured bytab pituitary surgery or in whom pituitary surgery is not an option. Osilodrostat has been evaluated in different multicentre phase II and III clinical studies, and has shown to have notable effects, such as significant reductions in cortisol secretion, associated with significant improvement in body weight, blood pressure, glucose metabolism, lipid profile, psychological status and quality of life. The favourable safety profile, combined with the relevant efficacy, could make osilodrostat suitable as medical treatment in several phases of the Cushing's syndrome treatment journey: before surgery, as preoperative treatment, or instead of surgery, in cases where surgery is not an option or refused, as first-line treatment; after surgery, in cases of persistent or recurrent disease, as second-line treatment; after second surgery or radiotherapy following pituitary surgery as bridging treatment waiting for the definitive disease control, as third-line treatment. Further real-world clinical experience data are needed to confirm the current knowledge.
PubMed: 38812665
DOI: 10.17925/EE.2024.20.1.8 -
TouchREVIEWS in Endocrinology Apr 2024Previous studies have suggested that corticotroph tumours are associated with the overexpression of cyclin E and that the inactivation of cyclin-dependent kinases, which...
Previous studies have suggested that corticotroph tumours are associated with the overexpression of cyclin E and that the inactivation of cyclin-dependent kinases, which activate cyclin E, may have antisecretory and antiproliferative effects. Seliciclib, also known as R-roscovitine, is a pituitary-targeting agent shown to inhibit the growth of corticotroph tumour cells via cyclin E and retinoblastoma protein-mediated pathways. A recent study investigated the role of seliciclib in regulating biochemical parameters in a small number of patients with Cushing's disease, providing preliminary data on its possible therapeutic effectiveness in treating this disorder.
PubMed: 38812663
DOI: 10.17925/EE.2023.20.1.4 -
Journal of Cerebrovascular and... May 2024A 50-year-old male patient with a history of transcranial surgery and subsequent radiotherapy for a pituitary adenoma presented with repetitive pulsatile nasal bleeding....
A 50-year-old male patient with a history of transcranial surgery and subsequent radiotherapy for a pituitary adenoma presented with repetitive pulsatile nasal bleeding. A right cavernous segment pseudoaneurysm was discovered on the angiogram, and the patient failed the balloon occlusion test. A Papyrus (Biotronik, Berlin, Germany) stent graft, which is approved for coronary interventions, was successfully deployed over a coaxial guiding system during the emergent treatment of the false aneurysm. The patient tolerated the procedure well and nasal bleeding did not recur after the procedure. At one-year angiographic follow-up, the stent graft was patent and there was no evidence of recanalization of the false aneurysm.
PubMed: 38812451
DOI: 10.7461/jcen.2024.E2023.11.007 -
Growth Hormone & IGF Research :... Jun 2024Acromegaly is a disorder associated with excessive levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). In general, GH/IGF-1 excess leads to... (Review)
Review
OBJECTIVE
Acromegaly is a disorder associated with excessive levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). In general, GH/IGF-1 excess leads to morphologic craniofacial and acral changes as well as cardiometabolic complications, but the phenotypic changes and clinical presentation of acromegaly differ across species. Here, we review the pathophysiology, clinical presentation and management of acromegaly in humans and cats, and we provide a systematic comparison between this disease across these different species.
DESIGN
A comprehensive literature review of pathophysiology, clinical features, diagnosis and management of acromegaly in humans and in cats was performed.
RESULTS
Acromegaly is associated with prominent craniofacial changes in both species: frontal bossing, enlarged nose, ears and lips, and protuberant cheekbones are typically encountered in humans, whereas increased width of the head and skull enlargement are commonly found in cats. Malocclusion, prognathism, dental diastema and upper airway obstruction by soft tissue enlargement are reported in both species, as well as continuous growth and widening of extremities resulting in osteoarticular compromise. Increase of articular joint cartilage thickness, vertebral fractures and spine malalignment is more evident in humans, while arthropathy and spondylosis deformans may also occur in cats. Generalized organomegaly is equally observed in both species. Other similarities between humans and cats with acromegaly include heart failure, ventricular hypertrophy, diabetes mellitus, and an overall increased cardiometabolic risk. In GH-secreting pituitary tumours, local compressive effects and behavioral changes are mostly observed in humans, but also present in cats. Cutis verticis gyrata and skin tags are exclusively found in humans, while palmigrade/plantigrade stance may occur in some acromegalic cats. Serum IGF-1 is used for acromegaly diagnosis in both species, but an oral glucose tolerance test with GH measurement is only useful in humans, as glucose load does not inhibit GH secretion in cats. Imaging studies are regularly performed in both species after biochemical diagnosis of acromegaly. Hypophysectomy is the first line treatment for humans and cats, although not always available in veterinary medicine.
CONCLUSION
Acromegaly in humans and cats has substantial similarities, as a result of common pathophysiological mechanisms, however species-specific features may be found.
Topics: Acromegaly; Cats; Humans; Animals; Insulin-Like Growth Factor I; Cat Diseases
PubMed: 38810595
DOI: 10.1016/j.ghir.2024.101595 -
A Rare Association of Autoimmune Hypophysitis With Seronegative Rheumatoid Arthritis: A Case Report.Cureus Apr 2024Autoimmune hypophysitis (AH) is an uncommon condition where there is inflammation of the pituitary gland which leads to hormonal imbalances. It is often associated with...
Autoimmune hypophysitis (AH) is an uncommon condition where there is inflammation of the pituitary gland which leads to hormonal imbalances. It is often associated with autoimmune diseases; however, a case is yet to be reported with an association of AH with seronegative rheumatoid arthritis (RA). We present a case of a 45-year-old female who complained of polyuria/polydipsia and rapid weight gain. An MRI of the head revealed enlargement of the pituitary gland, concerning for AH. Although she was initially treated for diabetes insipidus, she began reporting new complaints of joint pains and morning stiffness. She was clinically diagnosed with seronegative RA and improved with a trial of hydroxychloroquine. A repeat MRI showed improvement in the abnormal pituitary findings, and the patient was closely monitored with a multidisciplinary approach. Diagnosing and managing patients with AH are topics that are still being explored and researched as it is a relatively rare pathology. Consequently, we found the need to discuss the relationship of AH with seronegative RA and delve into the various diagnostic and treatment approaches.
PubMed: 38807817
DOI: 10.7759/cureus.59167 -
Lab Animal Jun 2024Researchers have advocated elevating mouse housing temperatures from the conventional ~22 °C to the mouse thermoneutral point of 30 °C to enhance translational...
Researchers have advocated elevating mouse housing temperatures from the conventional ~22 °C to the mouse thermoneutral point of 30 °C to enhance translational research. However, the impact of environmental temperature on mouse gastrointestinal physiology remains largely unexplored. Here we show that mice raised at 22 °C exhibit whole gut transit speed nearly twice as fast as those raised at 30 °C, primarily driven by a threefold increase in colon transit speed. Furthermore, gut microbiota composition differs between the two temperatures but does not dictate temperature-dependent differences in gut motility. Notably, increased stress signals from the hypothalamic-pituitary-adrenal axis at 22 °C have a pivotal role in mediating temperature-dependent differences in gut motility. Pharmacological and genetic depletion of the stress hormone corticotropin-releasing hormone slows gut motility in stressed 22 °C mice but has no comparable effect in relatively unstressed 30 °C mice. In conclusion, our findings highlight that colder mouse facility temperatures significantly increase gut motility through hormonal stress pathways.
Topics: Animals; Mice; Gastrointestinal Motility; Stress, Physiological; Male; Mice, Inbred C57BL; Temperature; Hypothalamo-Hypophyseal System; Gastrointestinal Microbiome; Pituitary-Adrenal System; Corticotropin-Releasing Hormone
PubMed: 38806681
DOI: 10.1038/s41684-024-01376-5 -
Archives of Medical Research Jun 2024Few data are available on adrenal morphology in patients with acute diseases, although it is known that endogenous glucocorticoids are essential for survival under...
BACKGROUND
Few data are available on adrenal morphology in patients with acute diseases, although it is known that endogenous glucocorticoids are essential for survival under stress conditions and that an adequate response is driven by activation of the hypothalamic-pituitary-adrenal (HPA) axis.
AIMS
The aim of this study was to assess adrenal morphology in patients with acute disease compared with patients with non-acute disease.
METHODS
This cross-sectional study included: 402 patients admitted to the emergency department (ED) for suspected SARS-CoV-2 infection (March-May, 2020) [main cohort]; 200 patients admitted to the ED for acute conditions (December 2018-February 2019) [control group A]; 200 outpatients who underwent radiological evaluation of non-acute conditions (January-February 2019) [control group B]. Chest and/or abdominal CT scans were reviewed to identify adrenal nodules or hyperplasia.
RESULTS
In the main cohort, altered adrenal morphology was found in 24.9% of the patients (15.4% adrenal hyperplasia; 9.5% adrenal nodules). The frequency of adrenal hyperplasia was higher both in the main cohort (15.4%) and control group A (15.5%) compared to control group B (8.5%; p = 0.02 and p = 0.03, respectively). In the main cohort, 14.9% patients died within 30 d. According to a multivariate analysis, adrenal hyperplasia was an independent risk factor for mortality (p = 0.04), as were older age (p <0.001) and active cancer (p = 0.01).
CONCLUSIONS
The notable frequency of adrenal hyperplasia in patients with acute diseases suggests an exaggerated activation of the HPA axis due to stressful conditions. The increased risk of short-term mortality found in patients with adrenal hyperplasia suggests that it may be a possible hallmark of worse prognosis.
Topics: Humans; COVID-19; Male; Female; Middle Aged; Emergency Service, Hospital; Aged; Cross-Sectional Studies; Hyperplasia; Adrenal Glands; Adult; SARS-CoV-2; Aged, 80 and over; Tomography, X-Ray Computed
PubMed: 38805767
DOI: 10.1016/j.arcmed.2024.103010 -
European Thyroid Journal Jun 2024Thyroid hormones have systemic effects on the human body and play a key role in the development and function of virtually all tissues. They are regulated via the...
INTRODUCTION
Thyroid hormones have systemic effects on the human body and play a key role in the development and function of virtually all tissues. They are regulated via the hypothalamic-pituitary-thyroid (HPT) axis and have a heritable component. Using genetic information, we applied tissue-specific transcriptome-wide association studies (TWAS) and plasma proteome-wide association studies (PWAS) to elucidate gene products related to thyrotropin (TSH) and free thyroxine (FT4) levels.
RESULTS
TWAS identified 297 and 113 transcripts associated with TSH and FT4 levels, respectively (25 shared), including transcripts not identified by genome-wide association studies (GWAS) of these traits, demonstrating the increased power of this approach. Testing for genetic colocalization revealed a shared genetic basis of 158 transcripts with TSH and 45 transcripts with FT4, including independent, FT4-associated genetic signals within the CAPZB locus that were differentially associated with CAPZB expression in different tissues. PWAS identified 18 and ten proteins associated with TSH and FT4, respectively (HEXIM1 and QSOX2 with both). Among these, the cognate genes of five TSH- and 7 FT4-associated proteins mapped outside significant GWAS loci. Colocalization was observed for five plasma proteins each with TSH and FT4. There were ten TSH and one FT4-related gene(s) significant in both TWAS and PWAS. Of these, ANXA5 expression and plasma annexin A5 levels were inversely associated with TSH (PWAS: P = 1.18 × 10-13, TWAS: P = 7.61 × 10-12 (whole blood), P = 6.40 × 10-13 (hypothalamus), P = 1.57 × 10-15 (pituitary), P = 4.27 × 10-15 (thyroid)), supported by colocalizations.
CONCLUSION
Our analyses revealed new thyroid function-associated genes and prioritized candidates in known GWAS loci, contributing to a better understanding of transcriptional regulation and protein levels relevant to thyroid function.
Topics: Humans; Thyroid Gland; Genome-Wide Association Study; Proteome; Hypothalamo-Hypophyseal System; Transcriptome; Thyrotropin; Thyroxine; Gene Expression Profiling
PubMed: 38805593
DOI: 10.1530/ETJ-24-0067 -
JCEM Case Reports Jun 2024Desmopressin is increasingly used for the diagnosis of Cushing disease (CD) since corticotropin-releasing hormone became unavailable. We report the case a 32-year-old...
Desmopressin is increasingly used for the diagnosis of Cushing disease (CD) since corticotropin-releasing hormone became unavailable. We report the case a 32-year-old man who presented with overt Cushing syndrome. Morning blood cortisol, ACTH, 1 mg dexamethasone suppression test, 24-hour urinary free cortisol, and bedtime salivary cortisol were highly variable, reaching markedly elevated values. Intravenous desmopressin administration produced no ACTH or cortisol increase. Pituitary magnetic resonance imaging, thoracic computed tomography, and DOTATATE positron emission tomography scan identified no lesion. Inferior petrosal sinus sampling (IPSS) with desmopressin stimulation resulted in elevated central-to-peripheral ACTH ratio and prolactin co-secretion, while peripheral ACTH remained stable. No corticotroph tumor was identified on pituitary surgery pathology. Hypercortisolism persisted postoperatively. Cabergoline was initiated, after which the patient rapidly developed transient severe adrenal insufficiency (AI). Bilateral adrenalectomy was performed in view of persistent hypercortisolism. This is an unusual case of petrosal sinus ACTH response to desmopressin without any peripheral response, suggesting a central source of ACTH. Thus, desmopressin should still be used during IPSS in patients with no peripheral response. It is unclear whether the AI episode resulted from a combination of nadir of cyclic hypercortisolism, partial apoplexy, and response to cabergoline of an occult corticotroph tumor.
PubMed: 38803508
DOI: 10.1210/jcemcr/luae092 -
Frontiers in Endocrinology 2024The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is frequent in lung cancer patients. Here, we report a case with persistent hyponatremia, which...
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is frequent in lung cancer patients. Here, we report a case with persistent hyponatremia, which suggested malignant SIADH and facilitated an early diagnosis of small cell lung cancer (SCLC). A combined radio-chemotherapy led to a partial remission and resolution of SIADH. An early relapse was indicated by reoccurring severe hyponatremia and increased copeptin levels, which were used as surrogate markers for the antidiuretic hormone (ADH). As palliative immunochemotherapy, together with fluid restriction and solute substitution, were unable to control hyponatremia, treatment with the ADH V2-receptor antagonist tolvaptan was initiated. Over time, the dose of tolvaptan needed to be increased, paralleled by a well-documented exponential increase of copeptin levels. In summary and conclusion, this is a rare case of a secondary failure to tolvaptan with unique documentary evidence of increasing copeptin levels. This observation supports the hypothesis that exceedingly high ADH levels may lead to competitive displacement of tolvaptan from the V2 receptor.
Topics: Humans; Tolvaptan; Inappropriate ADH Syndrome; Small Cell Lung Carcinoma; Lung Neoplasms; Antidiuretic Hormone Receptor Antagonists; Male; Hyponatremia; Aged; Treatment Failure; Middle Aged
PubMed: 38803472
DOI: 10.3389/fendo.2024.1382066