Decreased pituitary function and compensatory enlargement

By SWA

Introduction

The pituitary gland is a critical endocrine organ responsible for regulating the function of multiple hormonal systems through its secretion of tropic hormones. Decreased pituitary function, or hypopituitarism, can result from intrinsic gland pathology or secondary effects from surrounding structures. In some cases, a compensatory enlargement of the pituitary gland may occur as a physiological response to impaired function. This enlargement can be associated with a variety of underlying etiologies, including pituitary adenomas, autoimmune hypophysitis, hemorrhagic events (pituitary apoplexy), infiltrative or infectious processes, and radiation-induced injury. Enlargement of the gland may lead to mass effect symptoms, such as headache, visual field deficits, and cranial nerve involvement, particularly if the optic chiasm or cavernous sinus is affected. Early recognition and evaluation are essential, as both hormonal deficiencies and local compressive effects may require urgent medical or surgical intervention.

1. Decreased Pituitary Function (Hypopituitarism)

Hypopituitarism refers to a condition in which the pituitary gland fails to produce one or more of its hormones (partial hypopituitarism) or fails to produce any hormones (panhypopituitarism).

This underactivity can result from various causes, including:

  • Tumors

  • Inflammation

  • Infections

  • Radiation

  • Autoimmune disorders

  • Trauma or surgery

2. Compensatory Enlargement of the Pituitary Gland

When pituitary function is reduced, the gland may enlarge in an attempt to maintain hormonal output. This enlargement can be due to:

A. Pituitary Adenoma

  • A benign tumor of the pituitary gland.

  • Can be hormone-secreting (e.g., prolactinoma, ACTH-secreting tumor) or non-functioning (not secreting hormones, but causing compression of normal tissue).

  • Larger adenomas (>1 cm) are called macroadenomas and may compress the optic chiasm, causing visual disturbances, particularly bitemporal hemianopia (loss of peripheral vision).

  • Can also cause headaches due to local pressure effects.

B. Pituitary Apoplexy (Bleeding into the Pituitary Gland)

  • Acute bleeding, often into a tumor, can cause rapid enlargement and sudden symptoms:

    • Severe headache

    • Visual loss or double vision

    • Hormonal collapse (adrenal crisis, hypothyroidism)

  • A medical emergency.

C. Inflammation (Hypophysitis)

Inflammation of the pituitary gland can lead to gland enlargement and dysfunction. It may be:

  • Autoimmune (Lymphocytic hypophysitis):

    • Often seen in postpartum women or those with other autoimmune diseases.

    • Associated autoimmune conditions:

      • Hashimoto’s thyroiditis

      • Addison’s disease

      • Type 1 diabetes

      • Systemic lupus erythematosus (SLE)

      • Sjögren’s syndrome

  • Medication-induced hypophysitis:

    • Commonly associated with immune checkpoint inhibitors used in cancer therapy:

      • CTLA-4 inhibitors (e.g., ipilimumab)

      • PD-1/PD-L1 inhibitors (e.g., nivolumab, pembrolizumab)

D. Infections

Certain chronic infections can infiltrate or inflame the pituitary:

  • Tuberculosis

  • Sarcoidosis (granulomatous disease)

  • Syphilis

  • Fungal infections in immunocompromised individuals

  • These may mimic tumors and cause enlargement with hypopituitarism.

E. Radiation Therapy

  • Radiation for brain tumors or head/neck cancers can damage the pituitary gland over time, leading to both:

    • Hormonal deficiencies

    • Reactive (or fibrotic) enlargement

F. Other Rare Causes

  • Empty Sella Syndrome: A condition where the sella turcica (the bony cavity holding the pituitary) fills with cerebrospinal fluid, flattening or displacing the pituitary. Occasionally causes compensatory enlargement.

  • Cysts or congenital abnormalities

3. Symptoms of Pituitary Enlargement and Dysfunction

Pituitary enlargement affects nearby structures and hormone production:

Local Symptoms (Mass Effect):

  • Headaches

  • Visual disturbances (classically bitemporal hemianopia due to optic chiasm compression)

  • Nausea, vomiting (if acute or from increased intracranial pressure)

Hormonal Symptoms:

  • Fatigue, weakness

  • Weight gain or loss

  • Cold intolerance (from hypothyroidism)

  • Sexual dysfunction, infertility, amenorrhea

  • Low blood pressure, dizziness

  • Growth disturbances (in children)

  • Impaired stress response (adrenal insufficiency)

4. Medications Involved

A. Causing Pituitary Problems

  • Immune checkpoint inhibitors (e.g., ipilimumab, nivolumab) – can cause autoimmune hypophysitis.

  • Drugs interfering with dopamine (e.g., antipsychotics, metoclopramide) – may increase prolactin levels and cause secondary pituitary changes.

B. Treating Pituitary Disorders

  • Hormone replacement (as needed for deficiencies):

    • Hydrocortisone or prednisone for adrenal insufficiency

    • Levothyroxine for hypothyroidism

    • Sex hormones (testosterone, estrogen/progesterone)

    • Growth hormone (if deficient in children/adults)

    • Desmopressin (if diabetes insipidus occurs)

  • Dopamine agonists for prolactinomas:

    • Cabergoline or bromocriptine – shrink prolactin-secreting tumors

  • Immunosuppressive drugs for autoimmune hypophysitis (occasionally):

    • Corticosteroids are most commonly used

  • Surgical removal (transsphenoidal surgery) for large or symptomatic adenomas

5. Conclusion

Compensatory pituitary enlargement is a physiological response to underlying gland dysfunction or damage. It can arise from tumors, inflammation, infections, bleeding, or other causes. The gland tries to increase output, but depending on the cause and severity, hormone production may still fall short, requiring medical intervention.

Visual changes and headaches are red flags indicating mass effect, and hormonal evaluations, MRI imaging, and sometimes biopsy or surgery are part of diagnosis and treatment.

References: 

Endocrine Society Clinical Practice Guidelines
        e.g., "Diagnosis of Growth Hormone Deficiency in Adults" (2019)

        "Treatment of Hyperprolactinemia" (2011)
        https://www.endocrine.org/clinical-practice-guidelines
https://www.endocrine.org/search#q=Treatment%20of%20Hyperprolactinemia

 

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742

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