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Key Clinical Updates in Anterior Hypopituitarism

Opioid use disorder has become a common cause of functional hypopituitarism.

About 63% of long-term opioid (including methadone) users develop partial hypogonadotropic hypogonadism.

Opioid use also causes secondary adrenal insufficiency in about 15% of patients but is less likely to cause growth hormone or thyroid deficiency.


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

  • 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.


These tumors, also known as pituitary adenomas, can cause anterior hypopituitarism, particularly when they are large macroadenomas (1 cm or larger). Nonfunctioning pituitary neuroendocrine tumors 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, plasmacytoma, germ cell tumors, glioma, lymphomas, cysts (Rathke cleft, dermoid, epidermoid, arachnoid), meningioma, and hemangiopericytoma (an especially aggressive meningeal tumor). Hypothalamic hamartomas typically present in infancy with seizures but can cause precocious puberty. Chondrosarcomas and chordomas can involve the clivus and bones of the skull base. Vascular lesions include pituitary tumor apoplexy, acute Sheehan syndrome, cavernous sinus aneurysm, and subarachnoid hemorrhage. Inflammatory/infiltrative lesions include granulomatosis with polyangiitis, xanthomatosis, giant cell granuloma, Langerhans cell histiocytosis, sarcoidosis, syphilis, hypophysitis, and tuberculosis. Infectious lesions can be bacterial, fungal, or parasitic.


These lesions are usually from breast cancer (45%), particularly when HER2 positive; about 50% present over 10 years after the primary tumor. Lung cancer accounts for about 21% of pituitary metastases that typically present either before or within 1 year of the primary cancer. Pituitary metastases often present with visual loss or ophthalmoplegia, ACTH deficiency (71%), TSH deficiency (65%), diabetes insipidus (26%), or gonadotropin deficiency (88%).

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 ...

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