Hyperpituitarism

Understanding the complexities of endocrine disorders is a fundamental aspect of medical education. In this section, we will focus on various pathologies associated with the pituitary gland, including a detailed look at Multiple Endocrine Neoplasia type I, McCune-Albright syndrome, and different types of functional pituitary adenomas.

Multiple endocrine neoplasia type I (MEN I) is a syndrome characterized by tumors in multiple endocrine glands, notably the pituitary, pancreas, and parathyroid glands. In the context of the pituitary gland, MEN I often results in pituitary adenoma formation.

McCune-Albright syndrome affects the endocrine system through genetic mosaicism. Originating from a G-protein signaling mutation, the condition elevates cAMP levels, resulting in overactive endocrine tissue. The syndrome manifests as a triad of symptoms: unilateral café-au-lait macules, polyostotic fibrous dysplasia, and precocious puberty.

The most common functional pituitary adenoma is prolactinoma, characterized by overgrowth of lactotroph cells. Elevated prolactin suppresses gonadotropin-releasing hormone (GnRH) from the hypothalamus, reducing LH & FSH levels. This leads to hypogonadism secondary to hyperprolactinemia, causing amenorrhea & infertility in premenopausal women, as well as impotence & galactorrhea (rarely) in men. Treatment commonly involves D2 dopamine agonists such as cabergoline and bromocriptine, which curb prolactin production in lactotrophs.

The second most common functional pituitary adenoma is the growth hormone-producing adenoma, or GHoma. Growth hormone stimulates the liver to produce insulin-like growth factor-1 (IGF-1), resulting in clinical manifestations that differ depending on age. In children, rapid linear growth before the closure of epiphyseal plates results in pituitary gigantism. In adults, the syndrome manifests as acromegaly and leads to non-linear bone growth causing symptoms like frontal bossing, macrognathia, and enlarged hands & feet.

Acromegaly presents a range of complications including macroglossia, leading to upper airway obstruction and sleep apnea, as well as signs of masculinization like hirsutism in women. Joint issues arise from hypertrophic arthropathy due to stiffened synovial tissue. Organ enlargement, or visceromegaly, particularly affects the heart, liver, and thyroid. The condition is also associated with an increased risk of colon polyps & colon cancer. Elevated levels of growth hormone and insulin contribute to sodium and volume retention, causing hypertension. Cardiovascular issues such as heart failure, arrhythmia, and particularly aortic regurgitation may develop. Finally, the increase in gluconeogenesis from excess GH leads to hyperglycemia, contributing to the development of insulin resistance & type II diabetes.GH receptor antagonist such as cabergoline, pegvisomant, as well as octreotide a somatostatin analog.

A less common type of pituitary adenomas are thyrotroph adenomas, capable of producing thyroid-stimulating hormone (TSH). These adenomas cause secondary hyperthyroidism, characterized by elevated levels of both T4 and TSH. Chronic TSH secretion can also induce thyroid hypertrophy & hyperplasia, leading to goiter formation.

ACTH-producing pituitary adenomas cause chronic stimulation of the adrenal cortex, leading to increased cortisol production and eventually, hypercortisolism or Cushing's disease. Symptoms can include fat redistribution, thin skin, obesity, & insulin resistance.

Lastly, gonadotrophic pituitary adenomas are mostly non-functional and only manifest symptoms due to their mass effect, such as headaches and visual changes.