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  • Adrenocorticotropic hormone (ACTH) deficiency: reduced adrenal secretion of cortisol and epinephrine; aldosterone secretion remains intact.

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

  • Prolactin (PRL) deficiency: postpartum lactation failure.

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

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


Hypopituitarism can be caused by either hypothalamic or pituitary dysfunction. Patients with hypopituitarism may have single or multiple hormonal deficiencies. The anterior pituitary hormones are GH, PRL, ACTH, TSH, LH, and FSH. The posterior pituitary hormones are oxytocin and arginine vasopressin (AVP), also known as antidiuretic hormone (ADH). When one pituitary hormonal deficiency is discovered, others may be present.

1. Hypopituitarism with mass lesions

Lesions in the hypothalamus, pituitary stalk, or pituitary can cause hypopituitarism. Pituitary adenomas can cause anterior hypopituitarism, particularly when they are large macroadenomas (1 cm or more in diameter). Nonfunctioning pituitary adenomas are more likely than functioning pituitary adenomas to grow large enough to cause anterior hypopituitarism; they rarely cause diabetes insipidus. Pituitary adenomas are usually sporadic but 5% arise in familial tumor syndromes. Pituitary adenomas most frequently secrete PRL or (less commonly) GH or ACTH. Other mass lesions include craniopharyngioma, meningioma, germinoma, glioma, chordoma, metastatic lesions, and cysts (Rathke cleft, dermoid, arachnoid). Vascular lesions include pituitary tumor apoplexy, acute Sheehan syndrome, intrasellar carotid aneurysm, and subarachnoid hemorrhage. Inflammatory/infiltrative lesions include granulomatosis with polyangiitis, xanthomatosis, giant cell granuloma, Langerhans cell histiocytosis, sarcoidosis, syphilis, and tuberculosis. Infectious lesions can be bacterial, fungal, or parasitic.

Lymphocytic hypophysitis is an autoimmune disorder affecting the pituitary gland. It is 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 Hashimoto thyroiditis. Immune checkpoint inhibitor hypophysitis can be caused by several immunity-enhancing drugs, particularly the anti-CTLA-4 agents ipilimumab and tremelimumab (10–15%), as well as with the anti-PD-1 agents pembrolizumab and nivolumab. Symptoms of hypophysitis develop on average 9 weeks after beginning the medication and as late as 19 months after commencing therapy.

2. Hypopituitarism without mass lesions

Congenital combined hypopituitarism occurs in syndromes such as septo-optic dysplasia and in patients with various gene mutations (eg, PROP1 mutations) that cause a progressive loss of anterior pituitary function in childhood. Congenital hypogonadotropic hypogonadism can be caused by mutations in any of the many genes that control the production or release of gonadotropin-releasing hormone (GnRH), LH, or FSH. Hypogonadotropic hypogonadism also occurs with the syndrome of congenital adrenal hypoplasia. Congenital adrenal hypoplasia may be autosomal recessive or X-linked (due to a mutation in the DAX 1 gene), resulting in adrenal insufficiency in male infants ...

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