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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 deficiency: postpartum lactation failure

  • Thyroid-stimulating hormone (TSH) deficiency: causes secondary hypothyroidism

  • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) deficiency: cause hypogonadism and infertility in men and women

General Considerations

  • Caused by hypothalamic or pituitary dysfunction

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

Hypopituitarism with mass lesions

  • 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

    • Acute Sheehan syndrome

    • 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 about 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 (SLE) 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

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 of GnRH-synthesizing neurons from the olfactory bulb to the hypothalamus

      • Incidence in males, 1:10,000; in females, 1:50,000

    • Congenital GH deficiency occurs as an isolated pituitary hormone deficiency in about one-third of cases

  • Acquired hypopituitarism

    • Can result from

      • Cranial radiation therapy

      • Pituitary surgery

      • Encephalitis

      • Cerebral malaria

      • Hemochromatosis

      • Autoimmunity

      • Coronary artery bypass grafting (CABG)

    • Bexarotene chemotherapy causes a ...

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