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morbid obesity and the fear of sex steroid replacement exacerbating existing behavioural problems. Regarding the concern over obesity, our study shows the significant mortality in PWS and that, consistent with data from France ( 29 ) and the United
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
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Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
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Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
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alterations. Importantly, in MPHDs other major confounders must be taken into account. Both estrogens and GH influence thyroid hormone transport and/or metabolism and consequently interfere CeH management ( 33 , 60 ). Sex steroid and GH deficiencies can
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. However, other studies suggest that T2DM is a risk factor for testosterone deficiency and impaired sex steroid status ( 73 ). One large prospective study showed that the development of T2DM is a major driver of the age-related testosterone decline ( 74
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variants. The verification test results showed that 21.79% variants (17/78) were found to be de novo mutations. In primary gonadal/genital disorders subjects ( n = 48), SRD5A2 (steroid 5-alpha-reductase 2) and AR (androgen receptor) were the most
Endocrine Unit, Royal Victoria Infirmary, Newcastle upon Tyne, UK
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Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
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Endocrine Unit, Royal Victoria Infirmary, Newcastle upon Tyne, UK
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-type. In recent years, a few studies have demonstrated that adenovirus-mediated forced expression of SF1 could transform rodent and human adipose tissue or bone marrow-derived MSCs into steroidogenic cells, with the ability to produce multiple steroid
The Clatterbridge Cancer Centre, Wirral, UK
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Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
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Introduction
Immune checkpoint inhibitors can lead to thyroid dysfunction. However, the understanding of the clinical phenotype of ICI-induced thyroid dysfunction in the real-world population is limited. The purpose of this study was to characterise the clinical patterns of dysfunction and evaluate the demographic, biochemical and immunological features associated with this patient cohort.
Materials and methods
To characterise the longitudinal clinical course of thyroid dysfunction in patients from a single, UK regional cancer centre, a retrospective review of patients was conducted. Inclusion criteria included all patients treated with antiPD-1 checkpoint inhibitors (ICI), either as monotherapy (pembrolizumab/nivolumab) or in combination with a CTLA-4 inhibitor (ipilimumab). Patterns of toxicity were evaluated together with assessment of antibody titres.
Results
Over 16 months, thyroid dysfunction was seen in 13/90 and 3/13 patients treated with anti-PD1 monotherapy and in combination with ipilimumab, respectively. Patients either developed hyperthyroidism followed by hypothyroidism (12/16) or de novo hypothyroidism (4/16). Most patients were female (n = 11). All patients required thyroid replacement therapy. There was no relationship between clinical pattern of dysfunction and the presence of thyroid autoantibodies.
Conclusions
There are two distinct patterns of thyroid dysfunction in ICI-treated patients. Patients with thyroiditis develop subsequent hypothyroidism in the vast majority of cases. The potential benefit from steroids or other therapy to manage the hyperthyroid phase remains unclear. Early detection of these patients through appropriate monitoring will improve clinical management and early hormone replacement, reducing the symptomatic burden of hypothyroidism.
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Aim: To define functional and anatomical pituitary disease following ICI therapy and describe any change in pituitary function with time.
Methods: Retrospective observational audit of patients on ICI therapy in our centre between 2013 and 2023. We reviewed all patients on ICI therapy under the oncology department at University Hospital Plymouth, and identified individuals referred to endocrinology with suspected adrenal insufficiency. Patients were established on adrenal steroid replacement and subsequently underwent formal pituitary testing. Pituitary disease was evidenced by low ACTH, other pituitary dysfunction and/or abnormalities on pituitary imaging.
Results: 954 patients received ICI therapy during the study period, and 37 developed HPA axis dysfunction. Median interval of onset of symptoms was 4 months. There was no recovery in cortisol or ACTH for any individual on repeated testing. Other permanent anterior pituitary hormone defects were unusual. Hypophysitis associated with immunotherapy appears to specifically target corticotrophs with no evidence of recovery. There was a specific abnormality seen in MRI scans of 7 of 27 patients who had scans, appearing to be a particular feature of immune mediated hypophysitis. These were confined to the anterior aspect of the pituitary as striations and were not visible on any scans performed more than three months after disease onset.
Conclusion: These data show that immune related (IR) hypophysitis is a common complication of immune checkpoint inhibitor therapy. This may result in an imaging abnormality within the areas of the pituitary richest in corticotrophs. The endocrine consequence of this is a permanent defect in ACTH and therefore cortisol production.
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Université Pierre et Marie Curie, Sorbonne Université, Paris, France
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INSERM UMR_S933, Paris, France
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Université Pierre et Marie Curie, Sorbonne Université, Paris, France
INSERM UMR_S933, Paris, France
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isoenzyme 3b-HSD2 is an essential step for the biosynthesis of all steroids. Therefore, it plays a crucial role in aldosterone, cortisol and sex hormones production ( Fig. 1 ). Phenotypes encompass a continuum from mild-to-severe enzymatic deficiency. In the
National Hospital for Neurology and Neurosurgery, London, UK
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National Hospital for Neurology and Neurosurgery, London, UK
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function tests, clotting profile Indications for empirical steroid therapy in patients with pituitary apoplexy are haemodynamic instability, altered consciousness level, reduced visual acuity and severe visual field defects. Steroid replacement is
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feedback control of glucocorticoid maintenance and an association with metabolic syndrome (10, 11) . Little is known about steroid hormone availability and metabolism during the early postpartum period in infants. Fetal exposure to maternal cortisol is
