Trends in Endocrinology & Metabolism
OpinionThe Changing Clinical Spectrum of Hypophysitis
Section snippets
Hypophysitis: Actual and Future Prospective
Hypophysitis is a rare inflammatory disease of the pituitary gland and represents an emerging problem, as in recent years, an increased number of affected patients has been described. However, at the moment, no consensus for early diagnosis and management has been provided. For some years, the diagnosis of hypophysitis has been conducted on the basis of the histological detection of an inflammatory infiltration in the pituitary gland. According to the histological features of the pituitary
Epidemiology of PAH and IIH
Epidemiological data of PAH and IIH are not conclusive. The reported annual incidence of PAH is estimated as one case per 9 million inhabitants [26]. Females are predominantly affected by adenohypophysitis, and middle-aged males and children by infundibulo-neurohypophysitis 27., 28..
IIH frequency ranges from 0.7% to 15% of ICI-treated patients 29., 30., 31.. This different frequency may be influenced by different factors, such as the class of ICI, the use of ICI-associated treatments, duration
Physiopathology of PAH and IIH
The immune checkpoint is the gate regulating the immune response that is involved in maintaining immunological homeostasis and preventing the onset of autoimmune disease [43]. Programmed death (PD)-1 is one of the representative immune checkpoint molecules. It is mainly expressed on the surface of effector T cells in tumor or peripheral tissue, B cells, antigen-presenting cells, and natural killer cells. PD-1 can selectively bind to PD-1 ligand (PD-L)1 (CD274) or PD-L2 (CD273) on the cellular
Diagnostic Criteria of PAH and IIH
PAH and IIH are diagnosed in most cases through clinical criteria [47], as pathological analysis of the pituitary tissue is not performed in the absence of indications for surgery. Pituitary biopsy is not routinely performed because of its invasiveness and potential risk of further deterioration of pituitary function 12., 13., and remains limited to patients with an uncertain diagnosis and in cases with an indication of neurosurgical debulking, for reducing the obvious nerve compression 12., 13.
Hormone Replacement Therapy in PAH and IIH
As summarized in Table 1 59., 60., 61., 62., hormone replacement therapy should be administered according to the hypophysitis phase. Both in the acute and chronic phases of PAH and IIH, central hypoadrenalism, diabetes insipidus, and central hypothyroidism have to be managed. As a potential life-threatening condition, central hypoadrenalism has to be promptly treated, through the oral or parental administration of hydrocortisone, according to the patient’s clinical condition [63]. Similarly, in
Immunosuppressive Therapy in PAH and IIH
Immunosuppressive therapy should be considered only during the acute phase of hypophisitis in order to inhibit the inflammatory process, to reduce the compressive effects of the enlarged pituitary gland, and to avoid the development of glandular fibrosis that may cause irreversible hypopituitarism.
Glucocorticoids are considered as a first-line option for immunosuppressive treatment. Therapeutic schemes described in the literature are based on low or high doses of glucocorticoids (prednisolone
PAH and IIH Management
PAH and IIH represent a complex scenario that requires a multidisciplinary approach for diagnosis, treatment, and follow-up. As summarized in Figure 3, PAH diagnosis should be conducted according to the clinical findings, in the appropriate clinical context. Pituitary MR images play a central role in diagnosis, through the exclusion of focal pituitary lesions. Similarly, the etiological diagnosis of hypophysitis requires a multidisciplinary management. At diagnosis, infectious disease
Concluding Remarks and Future Perspectives
The heterogeneity of hypophysitis definition and the diagnostic/therapeutic protocols makes the evaluation and management of hypophysitis difficult, resulting in increased morbidity, worse outcomes, or even death. Cases of spontaneous partial and complete recovery have been documented. Univocal diagnostic criteria, treatment protocols, and outcome definitions are required for prompt diagnosis and treatment and for appropriate management of immunotherapy, avoiding life-threatening conditions and
Acknowledgments
The authors wish to thank the Oncology Team of Istituto Dermatopatico dell’Immacolata in Rome, and Prof. Alessandro Scoppola for collaboration and the courtesy of sharing the information and images of the clinical case reported.
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Executive summary of the consensus document on hypophysitis of the Neuroendocrinology Area of Knowledge of the Spanish Society of Endocrinology and Nutrition
2023, Endocrinologia, Diabetes y NutricionHypophysitis
2022, Endocrine PracticeCitation Excerpt :Therefore, comparisons of the outcomes of treatment options should be cautiously interpreted. Furthermore, stages at presentation (acute or chronic) may play a part in responding to a treatment, with chronic disease and resultant scarring thought to be less responsive to immunosuppressive regimens.2,32 At the time of presentation, patients with clinical signs and symptoms in association with radiologic findings suggestive of hypophysitis should be assessed for pituitary hormone deficits while ruling out secondary causes, as suggested in the Table.
The changing clinical spectrum of endocrine adverse events in cancer immunotherapy
2022, Trends in Endocrinology and MetabolismCitation Excerpt :Both anti-CTLA-4 and anti-PD-1 mAbs have been associated with thyroid dysfunction, hypophysitis, hypopituitarism, and insulin-dependent diabetes [42]. The epidemiological data on e-IRAEs are not conclusive because they are influenced by several factors such as study design, sample size, heterogeneity of the patient cohort, different subtypes of ICIs, and variable diagnostic criteria for endocrinopathies [21]. Most e-IRAEs can be well managed though a multidisciplinary approach between endocrinologists and oncologists that can ensure not only patient safety but also compliance with ICI treatment [21].
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