Necrotizing Infundibulo-Hypophysitis - A Rare Condition

Introduction

Hypophysitis is a rare pituitary gland and infundibulum inflammation, often caused by autoimmune, infiltrative, infectious, neoplastic, or unknown factors. Recent years have seen improved understanding and diagnosis of the condition, including new causes like IgG4-related disease, immunotherapy-induced Hypophysitis, and autoimmunity linked to tumors. The exact yearly incidence remains uncertain, but advancements in imaging, pathology, and awareness have increased reported cases. Distinguishing Hypophysitis from other pituitary conditions can be difficult due to similar symptoms shared with common adenomas and rare metastases.

What Is Necrotizing Infundibulo-Hypophysitis?

Hypophysitis refers to pituitary gland inflammation due to various underlying causes. The condition's diagnosis is complex, with many potential factors, including tumors, metastases, and lymphoproliferative diseases. As imaging shows, common symptoms include headaches, pituitary dysfunction, and gland enlargement. While autoimmune reasons are prevalent, other origins, like tumor inflammation, systemic illnesses, infections, or drugs, are possible. Emerging forms like IgG4-related and immunotherapy-induced Hypophysitis contribute to the expanding spectrum. Imaging typically shows gland enlargement and stalk thickening, but it's not always specific. Diagnosing Hypophysitis can be challenging, often requiring a biopsy to differentiate it from other causes.

A presumptive diagnosis is often possible without resorting to a biopsy. Thorough patient history and clinical examination are crucial to identify signs of underlying causes with systemic effects. Hormone replacement and, in certain instances, careful monitoring and follow-up imaging are recommended. High-dose glucocorticoids are primarily used to alleviate mass-related symptoms. They can yield positive results in autoimmune causes and lymphoproliferative diseases, making them unsuitable for differential diagnosis. Surgery might be needed to relieve mass pressure and attain a definitive diagnosis. Immunosuppressive treatment and radiation could become necessary for cases resistant to other interventions.

What Are the Causes and Types of Necrotizing Infundibulo-Hypophysitis?

Hypophysitis refers to a range of inflammatory conditions affecting the pituitary gland. It can impact different parts:

• The anterior pituitary (adenohypophysitis), infundibulum, and posterior pituitary (infundibulo-neurohypophysitis), or the entire pituitary (pan hypophysitis).

• The inflammation may sometimes extend into the hypothalamus or manifest as an isolated hypothalamus. Etiologically, Hypophysitis is classified as primary (autoimmune or other unknown causes) or secondary (resulting from local, systemic, infectious, neoplastic, or drug-related factors).

• Histological classification encompasses various types of Hypophysitis, such as lymphocytic, granulomatous, xanthomatous, IgG-4-related, necrotizing Hypophysitis, and mixed variations like lymphogranulomatous and xanthogranulomatous. Lymphocytic Hypophysitis (LHy) is generally the most prevalent form. Accurate categorization can be challenging at times due to overlapping pathological characteristics.

Etiology:

• Tumorous: Pituitary adenoma, Pituitary metastases.

• Ischemic: Sheehan syndrome.

• Thrombotic/Hypercoagulative: Antepartum necrosis of gestational diabetes, and septic shock.

• Autoimmune: Hypophysitis.

• Mechanical: Elevated intracranial pressure (secondary to subarachnoid hemorrhage, basilar artery thrombosis).

• Miscellaneous: Pituitary stimulation test.

• Spinal Anesthesia: Snake venom poisoning.

What Are the Symptoms of Necrotizing Infundibulo-Hypophysitis?

Typically, Hypophysitis manifests with symptoms stemming from pituitary deficiencies, occasionally accompanied by headaches and visual alterations due to the pressure exerted by an enlarged pituitary gland and infundibulum. Roughly 50% of individuals experiencing primary Hypophysitis encounter headaches, and 10 percent to 30 percent encounter visual disruptions caused by the mass effect.

The symptoms resulting from the loss of anterior and posterior pituitary hormones vary based on the cause and the extent of pituitary damage. Generally, the coexistence of anterior pituitary dysfunction and diabetes Insipidus (DI) indicates an inflammatory or infiltrative origin, craniopharyngiomas, or metastasis and is less likely in pituitary adenomas.

In lymphocytic Hypophysitis (LHy) and Hypophysitis induced by immunotherapy, the inflammatory process primarily impacts corticotrophs, followed by gonadotrophs and thyrotrophs. Notably, this hormone-impact pattern differs from that observed in pituitary adenomas, where corticotrophs are usually affected later in the progression.

Initial testing of pituitary function is essential for all patients. This includes 8 am cortisol measurement (or ACTH stimulation test), Thyroid-Stimulating Hormone (TSH), free thyroxine, prolactin, Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH) along with estradiol in premenopausal women or testosterone in men, insulin-like growth factor 1 (IGF-1), and assessment of serum sodium, plasma, and urine osmolarity if Diabetes Insipidus (DI) is suspected.

Notably, hyponatremia can be seen in cases of Adrenal Insufficiency (AI), severe hypothyroidism, and syndrome of inappropriate secretion of antidiuretic hormone, while hypernatremia may occur in uncompensated DI. The specific systemic characteristics tied to the root cause may differ across various types of Hypophysitis, contingent on the etiology and clinical context.

Some common symptoms include:

• Headaches: Often severe and persistent.

• Vision Changes: Blurred vision, visual field defects, or double vision.

• Hormonal Imbalances: These can include deficiencies in hormones produced by the pituitary gland, leading to symptoms such as fatigue, weakness, weight loss or gain, low blood pressure, and changes in menstrual cycles.

• Fatigue: Feeling tired and lacking energy.

• Nausea and Vomiting: Due to hormonal disruptions.

• Cognitive Changes: Memory problems, difficulty concentrating.

• Hormonal Deficiencies: Such as thyroid hormones, adrenal hormones, and reproductive hormones.

• Polyuria and Polydipsia: Increased urination and thirst.

• Mood Changes: Irritability, depression, or anxiety.

How Does Necrotizing Infundibulo-Hypophysitis Appear on a Radiograph?

Diverse imaging traits characterize Hypophysitis. The most prevalent MRI finding involves a thickened, straightened stalk. This can occur independently (infundibulo-neurohypophysitis) in around one-third of patients, or it might be coupled with mild to moderate symmetric gland enlargement in over 80% of cases. Typically, contrast uptake is intense and homogeneous, sometimes displaying irregularities. In primary Hypophysitis, about half of patients with an enlarged pituitary exhibit features similar to a pituitary macroadenoma. While pituitary adenomas might erode the sellar floor, Hypophysitis generally maintains its integrity.

Other indicators encompass the absence of a bright spot in the posterior pituitary due to the depletion of vasopressin granules in posterior pituitary Hypophysitis. Dural inflammation can lead to a dural tail sign akin to those seen in meningioma cases. In advanced stages, the pituitary gland may appear atrophied, and MRI might reveal a sellar arachnoidocele or an empty sella. Although no specific MRI features definitively confirm Hypophysitis, imaging can be diagnostic within the appropriate clinical context. For instance, the thickening of the stalk in a young woman who recently gave birth, presenting with headache and hypopituitarism, strongly suggests Lymphocytic Hypophysitis (LHy).

What Is the Diagnostic Procedure for Necrotizing Infundibulo-Hypophysitis?

Diagnosing necrotizing infundibulum-hypophysitis relies exclusively on examining the surgically removed pituitary tissue, given that clinical presentation and MRI appearance closely resemble more common hypophysitis forms. These prevalent forms include lymphocytic, granulomatous, and xanthomatous types. Patients with necrotizing infundibulo-hypophysitis experience sudden, severe headaches and develop lasting and comprehensive hypopituitarism. However, these features can also be observed in other non-secreting pituitary masses.

MRI shows symmetrical pituitary gland enlargement without hemorrhage signs alongside a thickened and pathologically enhancing stalk. Nevertheless, these features must be more specific to diagnose the condition before pituitary surgery. To confirm the diagnosis of necrotizing infundibulo-hypophysitis and other hypophysitis forms, the surgically removed pituitary specimen must undergo pathological examination.

The distinctive diagnostic hallmark of necrotizing infundibulo-hypophysitis is a notable infiltration of mononuclear cells within pituitary tissue accompanied by substantial necrosis. Pituitary tissue necrosis can manifest in various conditions, most prevalent in adenomas with apoplexy and Sheehan syndrome. Additionally, pituitary necrosis is observed in cases of gestational diabetes mellitus, Hypophysitis, and sporadically after pituitary stimulation tests, spinal anesthesia, or incidents of snake poisoning.

What Is the Treatment for Necrotizing Infundibulo-Hypophysitis?

Treatment aims to manage the inflammation, hormonal imbalances, and associated symptoms. The specific approach can vary based on the individual's condition and needs. It includes:

• Hormone Replacement Therapy: If the condition has led to deficiencies in hormones produced by the pituitary gland (such as thyroid hormones, cortisol, and reproductive hormones), hormone replacement therapy may be necessary to restore hormonal balance and alleviate symptoms.

• Anti-inflammatory Medications: Corticosteroids or other anti-inflammatory medications might be prescribed to reduce inflammation in the pituitary region and alleviate symptoms. These medications can help control the autoimmune response causing the condition.

• Surgery: In cases where there's significant compression of surrounding structures or suspicion of a tumor, surgical intervention might be considered. Surgery removes abnormal tissue, alleviates pressure on nearby structures, and improves symptoms.

• Monitoring and Follow-up: Regular monitoring of hormone levels, imaging studies, and overall health is essential to track the condition's progression and adjust treatment as needed.

• Supportive Care: Managing symptoms such as headaches, mood changes, and vision problems might involve supportive measures and medications.

Conclusion

Necrotizing infundibulo-hypophysitis represents a complex spectrum of inflammatory disorders affecting the pituitary gland, with various subtypes and diverse clinical presentations. Each type presents distinct characteristics on imaging and histological examination, from the more common lymphocytic and granulomatous forms to the rarer xanthomatous and necrotizing variants. The diagnosis of Hypophysitis demands a comprehensive approach, combining clinical evaluation, imaging studies, and often pathological examination of surgically removed tissue.