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  • 2020–2021 BCSC Basic and Clinical Science Course™

    Go to Academy Store Learn more and Purchase.

    1 Update on General Medicine

    Chapter 2: Endocrine Disorders

    Disorders of the Hypothalamic-Pituitary Axis

    The hypothalamus is the coordinating center of the endocrine system. It consolidates signals from higher cortical centers, the autonomic nervous system, the environment, and systemic endocrine feedback. The hypothalamus then delivers precise instructions to the pituitary gland, which releases hormones that influence most endocrine systems in the body. The hypothalamic-pituitary axis directly affects the thyroid gland, the adrenal gland, and the gonads; and it influences growth, milk production, and water balance.

    Table 2-1 Hypothalamic Neurohormones and Neurotransmitters Involved in Anterior Pituitary Function

    Table 2-1 outlines the major hypothalamic hormones and their actions on the anterior pituitary hormones. The hypothalamic hormones are released directly into a primary capillary plexus that empties into the hypophyseal portal venous circulation; they then travel down the pituitary stalk and bathe the anterior pituitary gland in a secondary capillary plexus. The hormones released by the hypothalamic neurons, therefore, reach their target cells rapidly and in high concentrations. This proximity allows a rapid, pulsatile response to signals between the hypothalamus and the anterior pituitary. The posterior pituitary is controlled by direct neuronal innervation from the hypothalamus rather than by blood-borne hormones. The main products of the posterior pituitary are vasopressin and oxytocin. Vasopressin (antidiuretic hormone) is primarily involved in controlling water excretion by the kidneys. Oxytocin stimulates uterine contractions during labor and delivery and milk ejection in lactation.

    Pituitary Adenomas

    Pituitary tumors account for 10%–15% of intracranial tumors. They are classified as microadenomas (<10 mm in the greatest diameter) or macroadenomas (≥10 mm in the greatest diameter). Typically benign, these tumors arise from hormone-producing cells and may be functionally active (ie, secrete large amounts of hormones) or inactive. The clinical presentation depends on what type of cell the tumor derives from and whether the tumor produces hormones. Any type of tumor may be clinically inactive and will become apparent only when it has enlarged enough to cause symptoms. Patients may present with headaches, visual symptoms such as visual field loss due to chiasmal compression, cranial neuropathies, and/or hypopituitarism from compression of normal pituitary tissue. (The ophthalmic effects of pituitary adenomas and other parasellar lesions are discussed in BCSC Section 5, Neuro-Ophthalmology.)

    Accounting for approximately 15% of pituitary tumors, somatotroph adenomas produce growth hormone, which can cause gigantism in prepubertal patients and acromegaly in adults. Acromegaly often develops insidiously over several years, and patients may present with headaches and visual symptoms due to enlargement of the adenoma before the diagnosis is recognized. Characteristic findings include an enlarged jaw, coarse facial features, and enlarged and swollen hands and feet. Patients may also have cardiac disease and diabetes mellitus in addition to the typical bone and soft-tissue changes.

    Lactotroph adenomas (prolactinomas) account for approximately 25% of symptomatic pituitary tumors. Hyperprolactinemia produces amenorrhea and galactorrhea in women and decreased libido and impotence in men. The symptoms tend to develop gradually in men, and patients may present with compression symptoms due to tumor enlargement before the hormonal effects are recognized.

    Thyrotroph adenomas are rare, accounting for less than 1% of pituitary tumors. They may cause hyperthyroidism, hypothyroidism, or no change in thyroid function, depending on how the TSH subunits are processed in the tumor cells. These tumors tend to be large macroadenomas, and patients may present with compressive symptoms in addition to any thyroid changes.

    Corticotroph adenomas account for approximately 15% of pituitary tumors. They are associated with Cushing syndrome, characterized by the classic features of centripetal obesity, hirsutism, and facial plethora. Fat deposits develop over the thoracocervical spine (buffalo hump) and temporal regions (moon facies). Psychiatric abnormalities occur in 50% of patients, and long-standing Cushing syndrome can cause osteoporosis. Patients bruise easily and have violet striae on the abdomen, upper thighs, and arms. Hypertension and glucose intolerance leading to diabetes mellitus can also occur. Cushing syndrome can also develop secondary to adrenal gland neoplasms and, most commonly, from iatrogenic administration of glucocorticoids.

    Gonadotroph adenomas (approximately 10% of pituitary tumors) may produce serum follicle-stimulating hormone and, in rare cases, luteinizing hormone. Affected patients present with hypogonadism related to gonadal downregulation. Gonadotropin-producing pituitary tumors may also be clinically inactive, and patients may present with compression symptoms.

    Accounting for approximately 15% of pituitary tumors, plurihormonal adenomas, as the name implies, produce more than 1 type of hormone. Common combinations include elevated growth hormone with prolactin and growth hormone with TSH.

    Null-cell adenomas (approximately 20% of pituitary tumors) do not have any pathologic markers to suggest a certain cell type and do not produce excess hormone. Most tumors that present with signs of enlargement and compression are gonadotroph or null-cell adenomas.

    Tumors of the pituitary gland are best diagnosed by means of contrast magnetic resonance imaging focused on the pituitary region. Endocrinologic testing is warranted when hypersecretion syndromes are suspected or when the patient has evidence of hypopituitarism. The treatment approach is complex and depends on a number of factors, including the size of the tumor and the nature of the hormonal activity. Treatment is discussed further in BCSC Section 5, Neuro-Ophthalmology.

    Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.

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