Autoimmune hypophysitis: a case of follow-up during the COVID-19 pandemic period

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INTRODUCTION

Hypophysitis, a rare inflammatory disorder that affects the pituitary gland and infundibulum, stems from autoimmune, infiltrative, infectious, neoplastic, or unknown causes. Its incidence is approximately 1 in 9 million individuals [1]. The clinical diagnosis of hypophysitis can be challenging because several pituitary lesions, including common pituitary adenomas and rare pituitary metastases, may clinically present with similar characteristics [2].

Magnetic resonance imaging (MRI) is crucial for diagnosing hypophysitis and categorizing it as follows: adenohypophysitis, which affects the anterior pituitary gland, and infundibulo-neurohypophysitis, which affects the pituitary stalk and posterior pituitary. Hypophysitis can be categorized as primary (autoimmune) or secondary due to local lesions (e.g., granulomas, cysts, and adenomas) or systemic diseases (e.g., sarcoidosis and Wegener’s granulomatosis) [3, 4].

Autoimmune hypophysitis (AH) is a diagnosis of exclusion that is made only after ruling out secondary causes of hypophysitis. All patients are evaluated for the exclusion of granulomatous vasculitis, sarcoidosis and Langerhans cell histiocytosis, according to the diagnostic criteria [5].

The following are the radiological signs of AH: pituitary enlargement (symmetric or asymmetric), pituitary enhancement pattern (homogeneous or heterogeneous), thickened stalk, extension of sellar mass (suprasellar and/or parasellar), hyperintensity of posterior pituitary gland on T1-weighted images, dural tail (identified or not identified), and parasellar signal intensity on T2-weighted images. The radiological signs can be mild and sometimes identifiable only if compared to previous imaging studies [6]. Different factors may have impact on clinical course of hypophysitis. Among them background treatment. These situations have not been understudied in the publications.

Herein, we aimed to elucidate the features of AH and influence on its course during the SARS-Cov-2 pandemic.

CASE PRESENTATION

Anamnesis

A 37-year-old female with a history of hyperprolactinemia (December 2019 level: 2144 mIU/L; normal range 109–557 mIU/L), underwent an MRI in May 2020 on the referral of her attending physician. At this stage, the patient did not have any complaints and was being treated symptomatically with the dopamine receptor agonist cabergoline (0.25 mg twice a week) to suppress prolactin secretion.

Diagnostic assessment

Contrast-enhanced MRI (Fig. 1) of the pituitary gland revealed a regular-sized pituitary gland (sagittal, 1.3 cm; vertical, 1.0 cm; and frontal, 2.0 cm) that was somewhat heterogeneous. The pituitary stalk was slightly deviated to the left. After gadolinium enhancement, a mild, uneven increase in the MR signal was observed at the center of the pituitary substance. Although the clinical and radiological findings were not consistent with hypophysitis, a follow-up MRI was recommended due to the heterogeneity of the hypophysis.

 

Fig. 1. MRI of the pituitary gland that was obtained on May 2, 2020. a) sagittal T1-weighted image, b) coronal T2-weighted image, and с) contrast-enhanced sagittal T1-weighted image. The size of the pituitary gland (*) was normal and slightly heterogeneous.

 

In September 2021, the patient did not present with any specific complaints other than headaches. Laboratory tests revealed a significant decrease in the prolactin levels (96.6 mIU/L). Furthermore, the follow-up MRI revealed an increase in the size and heterogeneity of the pituitary gland, which may be considered as early signs of hypophysitis (Fig. 2).

 

Fig. 2. MRI of the pituitary gland that was obtained on July 9, 2021. а) sagittal T1-weighted image, b) coronal T2-weighted image, and с) contrast-enhanced sagittal T1-weighted image. Note. There is a moderate increase in the size of the pituitary gland, an increase in the signal intensity in the pituitary gland substance in the T2-weighted images (*), and heterogeneous enhancement in the central region of the gland.

 

Differential diagnosis

The following were the differential diagnoses for the pituitary enlargement: an adenoma, which is more often hypovascular; a meningioma, with specific signs of dural spread; metastases without any information regarding the primary tumor; and several types of hypophysitis that cannot be differentiated on visualization [6].

Interventions

In December 2021, the patient developed severe COVID-19-associated pneumonia, resulting in damage to approximately 75% of the lung parenchyma. The patient was treated with corticosteroids and oxygen support. One month after being discharged from the hospital (January 2022), the patient presented to an endocrinologist with complaints of nausea, severe weakness, dizziness, and low blood pressure. Investigations revealed hypoprolactinemia, signs of hypothyroidism, and adrenal insufficiency.

Follow-up and outcomes

Given the change in the patient’s hormonal status and the deterioration of her condition, an MRI of the pituitary gland was advised (Fig. 3). The MRI showed no significant changes in the size or structure of the pituitary gland. However, there was a sharp thickening of the stalk and chiasm and increased heterogeneity of the structure. The patient was prescribed L-thyroxine 25 mcg daily to correct the hypothyroidism. Cabergoline was continued at the same dose. With this treatment, the patient reported an exacerbation of nausea, dizziness, and general weakness.

 

Fig. 3. MRI of the pituitary gland that was obtained on February 4, 2022. а) sagittal T1-weighted image, b) coronal T2-weighted image, and c) contrast-enhanced sagittal T1-weighted image. Note. Progression of the lesion is noted. Thickening of the chiasm (arrows) and infundibulum and increase in the size and structure of the pituitary gland were noted without pronounced dynamics when compared with the imaging study obtained on July 9, 2021.

 

In May 2022, the patient experienced a severe episode of hypotension (80/50 mmHg). Thus, the patient was diagnosed with adrenal insufficiency and admitted to the endocrinology department. The patient hormonal level test exhibited signs of hypothyroidism and adrenal insufficiency. Furthermore, the brain MRI revealed a marked increase in the size and heterogeneity of the pituitary gland (Fig. 4).

 

Fig. 4. MRI of the pituitary gland that was obtained on May 2, 2022. a) sagittal T1-weighted image, b) coronal T2-weighted image, and c) contrast-enhanced sagittal T1-weighted image. The dimensions of the pituitary gland are markedly enlarged (mainly due to the suprasellar component), its structure is heterogeneous, and its contours are uneven. The chiasm is compressed. There is a pronounced uneven thickening of the mucous membrane of the sphenoid sinus, exhibiting increased signal intensity on the T2-weighted image (*).

 

At this stage, the patient was treated with prednisone (10 mg in the morning and 5 mg in the evening) and cabergoline (0.25 mg twice a week). The patient improved with the treatment. The follow-up MRI on October 3, 2022, revealed significant improvement of size and heterogenity (Fig. 5).

 

Fig. 5. MRI of the pituitary gland that was obtained on October 3, 2022. а) sagittal T1-weighted image, b) coronal T2-weighted image, and c) contrast-enhanced sagittal T1-weighted image. The pituitary gland is not enlarged with heterogeneous contrast enhancement in the central regions. The chiasm is thickened, and its structure is moderately heterogeneous. These changes are positive in comparison with the findings of the previous MRI.

 

DISCUSSION

AH is a rare disease that should be suspected in patients with pituitary dysfunction or neurological/ophthalmological disorders (such as headaches and visual field defects) that is associated with typical neuro-radiological features [7]. Glucocorticoid therapy is pivotal in the treatment of AH. However, they should be cautiously used in patients being administered corticosteroids for other conditions such as rheumatological disorders or infections [8]. The clinical and MRI characteristics of hypophysitis are summarized in Table 1 [1, 9].

 

Table 1. Clinical and MRI characteristics of the hypophysitis

Types of hypophysitis	Clinical characteristics	MRI characteristics
• Primary: lymphocytic, granulomatous, xanthomatous, necrotizing, IgG4-related • Secondary: induced by immunomodulatory therapy, associated with sellar/chiasmal region masses	Clinical manifestations are non-specific: headache, visual disturbances (due to chiasmal compression), signs of hypopituitarism and/or diabetes insipidus. Lymphocytic, xanthomatous-more common in women. Granulomatous-equally affects both men and women. IgG4-associated — occurs in systemic diseases, accompanied by inflammatory lesions of the pancreas, biliary tract, retroperitoneum, mediastinum, thyroid gland, genitourinary tract, salivary and lacrimal glands, orbital structures, lymph nodes, aorta, pericardium, lungs, kidneys, skin, stomach, prostate, and ovaries. Induced by immunomodulatory therapy: the use of immuno-oncology drugs.	Symmetric pituitary enlargement. Heterogeneous adenohypophysis with cystic components. Intense, heterogeneous postcontrast enhancement. Possible dural tail sign. Suprasellar extension. Lymphocytic/granulomatous: thickened, inhomogeneous stalk. T2 hyperintensity of the chiasm and optic tracts. Xanthomatous: adenohypophysis involvement without stalk changes. Sellar-chiasmal masses: most commonly germ cell tumors, Rathke’s cleft cysts, or less frequently, craniopharyngiomas or adenomas.

 

The peculiarity of our case of AH is the evolution of the imaging findings. After “hypophysitis” was first suspected, specific treatment was not administered in the first 21 months. Therefore, the MR findings gradually progressed until the radiological and clinical manifestations were pronounced. The clinical and MRI findings quickly resolved after the administration of corticosteroids [10, 11].

The patient had a waxing and waning pattern of clinical and radiological symptoms (Fig. 6), with corresponding changes in the serum hormone levels. The patient’s condition improved with corticosteroid therapy. However, after discharge from the infectious disease hospital, the corticosteroid therapy for COVID-19 was discontinued, leading to a sharp deterioration in health. This indicates that the treatment of COVID-19 can affect the course of other underlying diseases, including AH. The evolution of the MRI changes is shown in (Fig. 6.)

 

Fig. 6. Contrast-enhanced T1-weighted coronal MR images of the pituitary gland obtained on a) May 2, 2020, b) July 9, 2021, c) February 4, 2022, d) May 2, 2022, and e) October 3, 2022. Over 1.5 years, the MRI findings pertaining to the pituitary gland in a patient with autoimmune hypophysitis evolved. First a, then an abrupt The size and heterogeneity of the pituitary gland increased, with the appearance of a non-contrasting area, probably due to necrosis (*). This increase was gradual at first (within 21 months: May 2, 2020 to February 4, 2022) and subsequently rapid (within three months: May 2, 2022 to October 3, 2022). The changes completely disappeared within 5 months after the administration of glucocorticosteroids.

 

CONCLUSION

This case report highlights the evolving MRI findings in a patient with AH, in whom delayed treatment intensified the radiological and clinical symptoms. Corticosteroid therapy promptly resolved the symptoms, highlighting its therapeutic role. Furthermore, in the postpandemic period, clinicians must consider the impact of COVID-19 on the course of other diseases such as AH.

ADDITIONAL INFORMATION

Funding source. This article was not supported by any external sources of funding.

Disclosure of interests. The authors declare that they have no relationships, activities or interests (personal, professional or financial) with third parties (commercial, non-commercial, private) whose interests may be affected by the content of the article, as well as no other relationships, activities or interests over the past three years that must be reported.

Authors’ contribution. E.N. Surovcev: examination of the patient, collection and analysis of literature data, writing the text of the manuscript; P.M. Zelter, Yu.S. Pyshkina: collection and analysis of literature data, writing and editing the text of the manuscript; A.V. Kapishnikov: analysis of literature data, editing the text of the manuscript. Thereby, all authors provided approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Consent for publication. Written consent was obtained from the patient for publication of relevant medical information and all of accompanying images within the manuscript in Digital Diagnostics journal.

About the authors

Evgeniy N. Surovcev

Samara State Medical University; Diagnostic and treatment center of International institution for biological systems named after Sergey Berezin

Email: evgeniisurovcev@mail.ru
ORCID iD: 0000-0002-8236-833X
SPIN-code: 5252-5661

MD, Cand. Sci. (Medicine)

Russian Federation, Samara; Tolyatti

Pavel M. Zelter

Samara State Medical University; Meir Hospital

Email: pzelter@mail.ru
ORCID iD: 0000-0003-1346-5942
SPIN-code: 3678-3932

MD, Cand. Sci. (Medicine)

Russian Federation, Samara; Kfar-Sava, Israel

Aleksandr V. Kapishnikov

Samara State Medical University

Email: a.kapishnikov@gmail.com
ORCID iD: 0000-0002-6858-372X
SPIN-code: 6213-7455

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Samara

Yuliya S. Pyshkina

Samara State Medical University

Author for correspondence.
Email: yu.pyshkina@yandex.ru
ORCID iD: 0000-0002-7241-6828
SPIN-code: 4225-1020

MD, Cand. Sci. (Medicine), Assistant Professor

Russian Federation, Samara

References

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