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For further information, see CMDT Part 26-01: Anterior Hypopituitarism

Key Features

Essentials of Diagnosis

  • Adrenocorticotropic hormone (ACTH) deficiency: low adrenal secretion of cortisol and epinephrine; normal aldosterone secretion

  • Growth hormone (GH) deficiency: in children, causes short stature; in adults, causes asthenia, obesity, and increased cardiovascular risk

  • Prolactin (PRL) deficiency: postpartum lactation failure

  • TSH deficiency: causes secondary hypothyroidism

  • LH and FSH deficiency: cause hypogonadism and infertility in men and women

General Considerations

  • Caused by either hypothalamic or pituitary dysfunction

  • May have single or multiple hormonal deficiencies of the anterior and posterior pituitary

Hypopituitarism with mass lesions

  • Lesions in the sellar or perisellar area may cause hypopituitarism by impingement on the hypothalamus, pituitary stalk, or pituitary

  • Nonfunctioning pituitary neuroendocrine tumors are more likely than functioning pituitary adenomas to grow large enough to cause anterior hypopituitarism; they rarely cause diabetes insipidus

  • Other mass lesions include

    • Craniopharyngioma

    • Plasmacytoma

    • Germ cell tumors

    • Glioma

    • Lymphomas

    • Cysts (Rathke cleft, dermoid, epidermoid, arachnoid)

    • Meningioma

    • Hemangiopericytoma

  • Vascular lesions include

    • Pituitary tumor apoplexy

    • Cavernous sinus aneurysm

    • Subarachnoid hemorrhage

  • Inflammatory/infiltrative lesions include

    • Granulomatosis with polyangiitis

    • Xanthomatosis

    • Giant cell granuloma

    • Langerhans cell histiocytosis

    • Sarcoidosis

    • Syphilis

    • Hypophysitis

    • Tuberculosis

  • Infectious lesions can be bacterial, fungal, or parasitic

  • Pituitary metastases

    • Often present with

      • Visual loss or ophthalmoplegia

      • ACTH deficiency (71%)

      • TSH deficiency (65%)

      • Diabetes insipidus (26%)

      • Gonadotropin deficiency (88%)

    • Usually from breast cancer (45%), particularly when HER2 positive

    • Lung cancer accounts for ~21% of pituitary metastases that typically present either before or within 1 year of the primary cancer

  • Lymphocytic hypophysitis

    • An autoimmune disorder affecting the pituitary gland

    • Characterized by infiltration of the infundibulum and pituitary by lymphocytes, macrophages, and plasma cells

    • Spontaneous lymphocytic hypophysitis is more common in women (71%) and most frequently presents during pregnancy or postpartum

    • The condition is often associated with other autoimmune conditions, such as systemic lupus erythematosus or autoimmune (Hashimoto) thyroiditis

  • Immune checkpoint inhibitor hypophysitis

    • Can be caused by several immunity-enhancing drugs, particularly the

      • Anti-CTLA-4 agents ipilimumab and tremelimumab

      • Anti-PD-1 agents pembrolizumab and nivolumab

    • Symptoms develop a median of 9 weeks after beginning ipilimumab and a median of 26 weeks after commencing an anti-PD-1 agent

  • Pituitary stalk thickening

    • Caused most frequently by autoimmune hypophysitis, neurosarcoidosis, or a congenital ectopic posterior pituitary

    • In children and teens, most commonly due to germ cell tumors, Langerhans histiocytosis, Rathke cleft cyst, or craniopharyngioma

    • Frequently causes central diabetes insipidus and ≥ 1 anterior pituitary hormone deficiencies

Hypopituitarism without mass lesions

  • Congenital hypopituitarism

    • Occurs in syndromes such as septo-optic dysplasia and in patients with various gene mutations that cause a progressive loss of anterior pituitary function in childhood

    • Prader-Willi syndrome

      • A genetic disorder where genes on the paternal chromosome 15 are deleted or unexpressed

      • Incidence is 1:15,000; both sexes are affected equally

    • Kallmann syndrome

      • Caused by various gene mutations that impair the development or migration ...

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