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Endocrine Connections Feb 2023High-dose glucocorticoids are associated with improved recovery of deficits in primary autoimmune hypophysitis (PAH), but optimal dosing, route, and duration are unclear.
OBJECTIVES
High-dose glucocorticoids are associated with improved recovery of deficits in primary autoimmune hypophysitis (PAH), but optimal dosing, route, and duration are unclear.
DESIGN
We reviewed literature for first-line glucocorticoid treatment in PAH until December 2021 and performed an individual patient data meta-analysis to analyze clinical, hormonal, and radiological outcomes with respect to route, dose, and duration (<6.5 vs 6.5-12 vs >12 weeks) of glucocorticoid treatment according to disease severity.
RESULTS
A total of 153 PAH patients from 83 publications were included. The median age at presentation was 41 (32.5-48) years with a female preponderance (70.3%). Visual field recovery was significantly better with i.v. (91.7%) as compared to oral (54.5%) route and high dose (100%) and very high dose (90.9%) as compared to medium dose (20%) of glucocorticoids. Corticotroph axis recovery was greater in i.v. (54.8% vs 28.1% oral, P = 0.033) route and increasing glucocorticoid dose group (0% vs 38.1% vs 57.1%), attaining statistical significance (P = 0.012) with very high-dose. A longer duration of treatment (>6.5 weeks) was associated with better corticotroph and thyrotroph recovery. The need for rescue therapy was lower with i.v. route (38% vs 17.5%, P = 0.012) and with increasing glucocorticoid doses (53.3% vs 34.3% vs 17.3%, P = 0.016). In severe disease, visual field and corticotroph axis recovery were significantly higher with i.v. route and very high-dose steroids. The adverse effects of glucocorticoids were independent of dose and duration of treatment.
CONCLUSIONS
Very high-dose glucocorticoids by i.v. route and cumulative longer duration (>6.5 weeks) lead to better outcomes and could be considered as first-line treatment of severe PAH cases.
PubMed: 36445257
DOI: 10.1530/EC-22-0311 -
Cureus Oct 2022Lymphocytic hypophysitis (LH) is a rare, autoimmune condition that presents with a range of symptoms that must garner the attention of medical practitioners. Clinically,...
Lymphocytic hypophysitis (LH) is a rare, autoimmune condition that presents with a range of symptoms that must garner the attention of medical practitioners. Clinically, it is characterized by symptoms of a compressive sellar mass with varying degrees of hypopituitarism due to chronic inflammatory infiltrate of the pituitary gland. It is often seen in women in their third trimester or postpartum and is associated with other autoimmune phenomena. Our case report describes a 73-year-old female with a past medical history of hypothyroidism and hypertension, who presented with continued intermittent dizziness, fatigue, and mild subjective hearing loss for the past several months. She was referred to the emergency department due to a sodium level of 119 and was initially diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH). The patient was treated accordingly; however, she failed to show signs of improvement. Due to her clinical presentation, imaging studies, and laboratory results, the patient was suspected to have LH, which was confirmed with the improvement of her symptoms after treatment with steroids. Because of the rare occurrence and possible atypical presentation of LH, this case illustrates the importance of maintaining a high index of clinical suspicion when diagnosing a patient with an unknown cause of hyponatremia, especially in patients with coexisting autoimmune disorders.
PubMed: 36397915
DOI: 10.7759/cureus.30178 -
Medicine Oct 2022Rheumatic diseases have been reported to sometimes involve the pituitary gland. This study aims to characterize the clinical features and outcomes of patients with...
Rheumatic diseases have been reported to sometimes involve the pituitary gland. This study aims to characterize the clinical features and outcomes of patients with rheumatic disease-associated hypophysitis. We used the electronic medical record system in our hospital to identify nine patients with pituitary involvement in rheumatoid disease. We summarized the clinical characteristics, radiographic findings, treatments, and clinical outcomes of the 9 patients. We also performed a systematic literature review of systemic lupus erythematosus (SLE) cases with pituitary involvement published in PubMed and Wanfang databases from 1995 to 2021, and eight patients with complete information were selected. In the nine-patient cohort, the median age was 54 years, and the spectrum of rheumatic diseases included immunoglobulin G4-related disease (IgG4RD) (4/9), SLE (2/9), vasculitis (2/9), and Sjögren syndrome (SS) (1/9). All patients had pituitary abnormalities on radiological assessment, 6 developed diabetes insipidus (DI), and 8 presented with anterior pituitary hormone deficiencies in the disease duration. All the patients had multisystem involvement. As compared to hypophysitis with IgG4RD (IgG4-H), the age at onset of hypophysitis with SLE (SLE-H) patients was younger [(30.4 ± 16.4) years vs. (56.0 ± 0.8) years] and the disease duration was shorter [(14.0 ± 17.5) months vs. (71.0 ± 60.9) months] (P < .05). All patients were managed with glucocorticoids (GC) in combination with another immunosuppressant, and the majority of patients improved within 4 months. Six patients achieved disease remission while four required at least one hormone replacement therapy. Hypophysitis is a rare complication secondary to a variety of various rheumatic diseases that can occur at any stage. GC combined with additional immunosuppressants could improve patients' symptoms; however some patients also required long-term hormone replacement therapy in pituitary disorders.
Topics: Humans; Middle Aged; Adolescent; Young Adult; Adult; Hypophysitis; Pituitary Diseases; Hypopituitarism; Pituitary Gland; Glucocorticoids; Rheumatic Diseases; Immunosuppressive Agents; Collagen Diseases; Lupus Erythematosus, Systemic; Autoimmune Hypophysitis
PubMed: 36316923
DOI: 10.1097/MD.0000000000031338 -
BMC Neurology Sep 2022Autoimmune hypothalamitis is a very rare neuroendocrine disorder that causes central diabetes insipidus, headache, visual impairment, and sometimes cognitive impairment....
BACKGROUND
Autoimmune hypothalamitis is a very rare neuroendocrine disorder that causes central diabetes insipidus, headache, visual impairment, and sometimes cognitive impairment. Autoimmune hypothalamitis may occur in association with autoimmune hypophysitis, including lymphocytic hypophysitis, or in isolation. It is not known whether autoimmune hypothalamitis and autoimmune hypophysitis are consecutive diseases.
CASE PRESENTATION
A 52-year-old woman developed autoimmune hypothalamitis 7 years after developing central diabetes insipidus due to lymphocytic hypophysitis, resulting in severe memory impairment. High-dose intravenous methylprednisolone therapy improved her cognitive function and decreased the size of the lesion.
CONCLUSION
This case presented a unique clinical course, with a long period of time between the onset of autoimmune hypopituitaritis and the development of autoimmune hypothalamitis.
Topics: Autoimmune Hypophysitis; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diabetes Mellitus; Female; Humans; Hypopituitarism; Magnetic Resonance Imaging; Memory Disorders; Methylprednisolone; Middle Aged
PubMed: 36175850
DOI: 10.1186/s12883-022-02891-z -
European Journal of Endocrinology Dec 2022Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment but are associated with significant autoimmune endocrinopathies that pose both diagnostic and...
Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment but are associated with significant autoimmune endocrinopathies that pose both diagnostic and treatment challenges. The aim of this guideline is to provide clinicians with the best possible evidence-based recommendations for treatment and follow-up of patients with ICI-induced endocrine side-effects based on the Grading of Recommendations Assessment, Development, and Evaluation system. As these drugs have been used for a relatively short time, large systematic investigations are scarce. A systematic approach to diagnosis, treatment, and follow-up is needed, including baseline tests of endocrine function before each treatment cycle. We conclude that there is no clear evidence for the benefit of high-dose glucocorticoids to treat endocrine toxicities with the possible exceptions of severe thyroid eye disease and hypophysitis affecting the visual apparatus. With the exception of thyroiditis, most endocrine dysfunctions appear to be permanent regardless of ICI discontinuation. Thus, the development of endocrinopathies does not dictate a need to stop ICI treatment.
Topics: Humans; Immune Checkpoint Inhibitors; Neoplasms; Endocrine System Diseases; Hypophysitis; Drug-Related Side Effects and Adverse Reactions
PubMed: 36149449
DOI: 10.1530/EJE-22-0689 -
AJNR. American Journal of Neuroradiology Sep 2022Granulomatous hypophysitis is a rare inflammatory condition of the pituitary gland with an imaging appearance that can overlap with that of pituitary adenoma.... (Review)
Review
BACKGROUND AND PURPOSE
Granulomatous hypophysitis is a rare inflammatory condition of the pituitary gland with an imaging appearance that can overlap with that of pituitary adenoma. Differentiating the two before surgical resection can have important treatment implications. The purpose of our study was to determine whether it was possible to differentiate between granulomatous hypophysitis and pituitary adenoma on the basis of diffuse enhancing infrasellar basisphenoid bone marrow.
MATERIALS AND METHODS
We present 3 cases, initially thought to be pituitary adenomas, that were pathology-proved granulomatous hypophysitis. The preoperative MR images were reviewed for diffuse, enhancing infrasellar basisphenoid bone marrow. For comparison, we reviewed 100 cases of pathology-proved pituitary adenoma for the same finding. Additionally, imaging findings including the sphenoid sinus pneumatization pattern, clinical history, laboratory values, and pathology results were reviewed.
RESULTS
All 3 cases of granulomatous hypophysitis had diffuse enhancing infrasellar basisphenoid bone marrow. Conversely, this was not seen in any of the 100 pituitary adenomas. The patients with granulomatous hypophysitis were all women. Two patients had idiopathic granulomatous hypophysitis, and 1 had secondary granulomatous hypophysitis with sarcoidosis. Of the 100 patients with pituitary adenomas, 67 were women. The basisphenoid pneumatization patterns was as follows: 15 (type 2), 40 (type 3), and 45 (type 4).
CONCLUSIONS
We present 3 cases of granulomatous hypophysitis with diffuse enhancement of the infrasellar basisphenoid bone marrow that was not seen in our 100 cases of pituitary adenomas. This imaging feature may be valuable for suggesting a diagnosis of granulomatous hypophysitis and avoiding surgical resection of what might otherwise be misdiagnosed as a pituitary adenoma.
Topics: Humans; Female; Male; Pituitary Neoplasms; Diagnosis, Differential; Hypophysitis; Pituitary Gland; Autoimmune Hypophysitis; Magnetic Resonance Imaging
PubMed: 36007945
DOI: 10.3174/ajnr.A7618 -
Endokrynologia Polska 2022Isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is a rare pituitary disorder characterized by decreased secretion of ACTH, leading to cortisol deficiency,...
Isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is a rare pituitary disorder characterized by decreased secretion of ACTH, leading to cortisol deficiency, with normal secretion of other pituitary hormones. Diagnostics remains a challenge due to variable and nonspecific clinical presentation: weakness, weight loss, and low blood pressure. Hyponatremia and anemia are typical abnormalities in basic laboratory tests. Diagnostic procedures for IAD are based on results of low morning cortisol with low/normal ACTH concentrations, with flat response of these hormones in dynamic tests [with insulin/glucagon/corticotropin-releasing hormone (CRH)]. There is also no cortisol response to Synacthen during the standard (not extended) test duration. Several aetiologies lead to the development of IAD. The congenital form is typical of childhood onset. In adults, autoimmune aetiology prevails, including lymphocytic hypophysitis, and rarer - pituitary injury or other lesions in the gland. IAD has recently been demonstrated as a complication in patients receiving therapy with immune checkpoint inhibitors. Also, in the case of IAD, paraneoplastic autoimmune hypophysitis should be considered. Next, alcohol abuse has been reported to be a reason of IAD in single cases. Treatment with oral hydrocortisone usually causes significant improvement. As an example, we present 2 patients diagnosed with IAD. Both were older males, with history of alcohol abuse, long lasting hyponatremia, and weakness. Their clinical state normalized after receiving replacement therapy with hydrocortisone.
Topics: Adrenocorticotropic Hormone; Adult; Alcoholism; Endocrine System Diseases; Genetic Diseases, Inborn; Humans; Hydrocortisone; Hypoglycemia; Hyponatremia; Male; Pituitary Diseases
PubMed: 35971928
DOI: 10.5603/EP.a2022.0056 -
Neuropathology : Official Journal of... Feb 2023Granulomatous hypophysitis is a rare and poorly understood condition. Although certain cases are treated as primary pituitary autoimmune disorders, rare cases may be...
Granulomatous hypophysitis is a rare and poorly understood condition. Although certain cases are treated as primary pituitary autoimmune disorders, rare cases may be associated with pituitary neuroendocrine tumours (PitNETs) and systemic inflammatory diseases. Here, we report a case of a 47-year-old man that underwent endoscopic trans-sphenoidal excision of a pituitary mass diagnosed as PitNET. On histologic evaluation, the neoplasm showed an admixture of granulomas with extensive inflammatory infiltrate and lactotroph PitNET/adenoma. Careful anamnestic examination revealed a diagnosis of Crohn's disease 20 years prior. Although rarely done, both PitNET and Crohn's disease may be associated with granulomatous hypophysitis, and our patient had both conditions. During the 6-year follow-up, PitNETs and hypophysitis did not recur, while Crohn's disease was only partially controlled by medical therapy. To our knowledge, this is the first description of association of granulomatous hypophysitis, PitNET and Crohn's disease.
Topics: Male; Humans; Middle Aged; Crohn Disease; Lactotrophs; Neoplasm Recurrence, Local; Pituitary Neoplasms; Hypophysitis; Prolactinoma
PubMed: 35949102
DOI: 10.1111/neup.12857 -
Frontiers in Oncology 2022Blockade of immune checkpoints transformed the paradigm of systemic cancer therapy, enabling substitution of a cytotoxic chemotherapy backbone to one of... (Review)
Review
Blockade of immune checkpoints transformed the paradigm of systemic cancer therapy, enabling substitution of a cytotoxic chemotherapy backbone to one of immunostimulation in many settings. Invigorating host immune cells against tumor neo-antigens, however, can induce severe autoimmune toxicity which in many cases requires ongoing management. Many immune-related adverse events (irAEs) are clinically and pathologically indistinguishable from inborn errors of immunity arising from genetic polymorphisms of immune checkpoint genes, suggesting a possible shared driver for both conditions. Many endocrine irAEs, for example, have analogous primary genetic conditions with varied penetrance and severity despite consistent genetic change. This is akin to onset of irAEs in response to immune checkpoint inhibitors (ICIs), which vary in timing, severity and nature despite a consistent drug target. Host contribution to ICI response and irAEs, particularly those of endocrine origin, such as thyroiditis, hypophysitis, adrenalitis and diabetes mellitus, remains poorly defined. Improved understanding of host factors contributing to ICI outcomes is essential for tailoring care to an individual's unique genetic predisposition to response and toxicity, and are discussed in detail in this review.
PubMed: 35912205
DOI: 10.3389/fonc.2022.894015 -
Digestive Diseases and Sciences Sep 2022
Topics: Autoimmune Diseases; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Cholangitis; Cholangitis, Sclerosing; Diagnosis, Differential; Humans; Hypophysitis; Immunoglobulin G4-Related Disease
PubMed: 35790701
DOI: 10.1007/s10620-022-07564-y