26-01: Anterior Hypopituitarism

ESSENTIALS OF DIAGNOSIS

GENERAL CONSIDERATIONS

The anterior pituitary hormones are GH, PRL, ACTH, TSH, LH, and FSH. The hypothalamus synthesizes hormones that regulate anterior pituitary secretion, including corticotropin-releasing hormone (CRH), growth hormone–releasing hormone, gonadotrophin-releasing hormone (GnRH), thyrotropin-releasing hormone, and somatostatin. The hypothalamus also secretes dopamine that inhibits PRL secretion. These hypothalamic regulatory hormones are transported by a portal venous system down the pituitary stalk to the anterior pituitary. The hypothalamus also synthesizes oxytocin and arginine vasopressin (AVP), also known as ADH. Nerves from the hypothalamus carry oxytocin and AVP to the posterior pituitary, where they are stored and released. Hypopituitarism can be caused by either hypothalamic or pituitary dysfunction. Patients with hypopituitarism may have single or multiple hormonal deficiencies.

1. Hypopituitarism with mass lesions

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

A. PITUITARY NEUROENDOCRINE TUMORS

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.

B. PITUITARY METASTASES

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%).

C. OTHER MASS LESIONS

These 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.

D. VASCULAR LESIONS

These lesions include pituitary tumor apoplexy, cavernous sinus aneurysm, and subarachnoid hemorrhage.

E. INFLAMMATORY/INFILTRATIVE LESIONS

These include granulomatosis with polyangiitis, xanthomatosis, giant cell granuloma, Langerhans cell histiocytosis, sarcoidosis, syphilis, hypophysitis, and ...