Pathophysiology
Summary
The endocrine system relies heavily on the hypothalamus, which functions in conjunction with the pituitary gland via the hypophyseal portal system to maintain hormonal balance throughout the body. Any pathology affecting these structures can result in hormonal imbalances with systemic repercussions. Hypopituitarism occurs when there is a deficiency in hormones released by the anterior pituitary gland, and may stem from either anterior pituitary dysfunction or hypothalamic dysfunction.
Anterior pituitary dysfunction is the most common etiology of hypopituitarism, and results deficiency in hormones secreted from the anterior pituitary like follicle-stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), prolactin, and growth hormone (GH). There can be several underlying causes for hypopituitarism, and they generally relate to either hypothalamic or pituitary dysfunction.
The most common cause of hypopituitarism in adults is a pituitary adenoma, which is a space-occupying lesion in the sella turcica that compresses the normal pituitary tissue. This can lead to pressure necrosis and result in hypopituitarism. Pituitary adenomas can present with symptoms such as headache due to compression of surrounding structures, or vision disturbances like bitemporal hemianopsia due to compression of the optic chiasm. Pituitary apoplexy is a form of acute hypopituitarism resulting from spontaneous hemorrhage of the pituitary gland—often from an enlarging pituitary adenoma— and presents with a sudden severe headache, visual disturbances, and cardiovascular collapse (decreased ACTH).
Hypopituitarism can also develop in the the postpartum period. During pregnancy, elevated estrogen levels induce hyperplasia of prolactin-secreting cells, leading to an increased pituitary size while the vascular supply to the pituitary remains unchanged, making it susceptible to ischemic injury. Sheehan syndrome arises due to acute blood loss during childbirth, causing ischemic necrosis of the enlarged pituitary. This condition manifests as an absence of lactation & resumption of menses in the postpartum period, attributable to hypopituitarism leading to decreased levels of prolactin, FSH, and LH.
Another condition associated with pregnancy is lymphocytic hypophysitis. This autoimmune disorder causes inflammation and necrosis of the pituitary gland, resulting in hypopituitarism. Histologically, it is characterized by abundant cells with blue nuclei due to lymphocyte infiltration. Treatment typically involves the administration of corticosteroids.
Primary empty sella syndrome is an anatomic defect leads to the extension of the dura into the sella, causing pressure atrophy of the pituitary tissue, subsequently leading to hypopituitarism. On the other hand, secondary empty sella syndrome is usually post-treatment, caused by radiation, injury, or surgery leading to regression of the pituitary gland.
Finally, injury to the hypothalamus can impair its ability to communicate with the anterior pituitary. The secretion of the hypothalamic hormones thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH), which function as the ‘go’ signal for the anterior pituitary, can be disrupted by various factors like traumatic brain injury, brain tumors, radiation therapy, or stroke—potentially leading to hypopituitarism.
Lesson Outline
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FAQs
The hypophyseal portal system is a vascular network that facilitates the transfer of hormones from the hypothalamus to the anterior pituitary gland. The hypothalamus releases ‘releasing hormones’ that act as signals for the anterior pituitary to secrete its own hormones into the peripheral circulation. In cases of hypopituitarism, a deficiency in these releasing hormones from the hypothalamus can lead to reduced hormone output from the anterior pituitary, resulting in hypopituitarism.
Brain tumors affecting the hypothalamus can disrupt the normal secretion of releasing hormones, leading to hypopituitarism. This occurs because the anterior pituitary gland relies on these hormones to regulate its own secretion. In the pituitary, tumors like pituitary adenomas—common tumors in or near the pituitary gland—can exert pressure on the gland, causing tissue necrosis and subsequently hypopituitarism.
Craniopharyngiomas are benign neoplasms that often occur in the pituitary stalk. These tumors can induce hypopituitarism by exerting pressure on the pituitary gland, causing tissue necrosis. In addition to hypopituitarism, craniopharyngiomas may cause headaches and vision issues due to their impact on nearby structures, such as the optic chiasm.
Sheehan's syndrome occurs in women who experience significant blood loss during childbirth. The condition leads to ischemic necrosis of the pituitary gland, which enlarges during pregnancy due to elevated estrogen levels but does not receive a corresponding increase in blood supply. The result is hypopituitarism, manifesting as a lack of lactation post-delivery and failure of menstrual cycles to resume.
Lymphocytic hypophysitis is an autoimmune disorder that targets the pituitary gland, causing inflammation and tissue necrosis. This condition often occurs during late pregnancy or the postpartum period and leads to hypopituitarism by destroying pituitary tissue. Treatment for this condition usually involves corticosteroids to manage inflammation and prevent further tissue damage.
