Hypopituitarism, Anterior

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 ...