The pituitary gland, often called “the master gland” is a small pea-sized endocrine gland attached to the base of the brain, just below the hypothalamus. It is the principal gland of the endocrine system that orchestrates a state of metabolic equilibrium among the various organs of the human body.

The pituitary gland consists of two morphologically and functionally distinct regions: the anterior pituitary lobe (adenohypophysis) and the posterior pituitary lobe (neurohypophysis). The hypothalamus predominantly regulates the production and secretion of most pituitary hormones.

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What Is the Anterior Pituitary?

The anterior pituitary (AP), also known as the adenohypophysis, constitutes about 80% of the pituitary gland. The anterior pituitary produces and releases over five different endocrine hormones that play a crucial role in regulating various bodily functions, including growth, reproduction, metabolism, and stress. The secretion of these hormones is controlled by both stimulatory and inhibitory hypothalamic-releasing factors. These hormones include:

Growth Hormone (GH)

• Stimulates the growth of almost all tissues of the body, its principal targets are bones and skeletal muscles (1).

Prolactin (PRL)

• The hypothalamic influence is both stimulatory (Prolactin-releasing Hormone; PRH) and inhibitory (Dopamine) on the secretion of Prolactin from the AP.
• Prolactin stimulates the growth and development of the mammary glands and consequently stimulates milk production in lactating women. 

Follicle-stimulating Hormone (FSH) and Luteinizing Hormone (LH)

• Act on the reproductive system (ovaries and testes) and regulate the production of sex hormones.
• In females, FSH stimulates the growth and development of follicles in preparation for ovulation and secretion of estrogen. LH triggers ovulation and stimulates the secretion of progesterone (1).
• In males, FSH is crucial for spermatogenesis and LH stimulates the secretion of testosterone. 

Thyroid-stimulating Hormone (TSH)

• Stimulates the thyroid gland to synthesize thyroid hormones - triiodothyronine [T3] and thyroxine [T4].

Adrenocorticotropic Hormone (ACTH)

• Stimulates the adrenal cortex to produce cortisol to help regulate the stress response.

What Is the Pituitary Gland?

The pituitary gland is vital to the human body and essential for sustaining life. It is the key regulator of homeostasis in our body through intricate physiological signaling between the hypothalamus and peripheral organs. 

This “master gland” is located at the base of the brain, cradled by a tiny protective bony cavity named the sella turcica. The pituitary gland has two anatomically and functionally distinct lobes: the anterior pituitary lobe (or adenohypophysis) and the posterior pituitary lobe (or neurohypophysis).

Pituitary Gland Function

The pituitary gland produces and secretes hormones under the regulation of stimulatory and inhibitory neurohormones secreted by the hypothalamus. The hormones released by the pituitary gland have a direct impact on the target organs and are responsible for regulating important physiological processes such as growth, reproduction, metabolism, and response to stress.

What Hormones Does the Pituitary Gland Secret?

The anterior pituitary lobe produces and secretes the following hormones:

• Growth Hormone (GH): stimulates the growth of cells in the body (particularly bone and skeletal muscles).
• Prolactin (PRL): stimulates the growth of the mammary glands and produces milk in lactating women.
• Follicle-stimulating Hormone (FSH) and Luteinizing Hormone (LH): regulate the production of sex hormones from the ovaries and testes (estrogen and progesterone in females, and testosterone in males) involved in ovulation and spermatogenesis, respectively.
• Thyroid-stimulating Hormone (TSH): acts on the thyroid gland to stimulate the release of T3 and T4 (2) which in turn regulates metabolism, energy production, and maintenance of basal body temperature.
• Adrenocorticotropic Hormone (ACTH): facilitates the release of cortisol from the adrenal cortex in response to stress. 

The posterior pituitary lobe secretes the following two hormones: 

• Oxytocin: stimulates milk ejection from the mammary glands in response to suckling by the contraction of myoepithelial cells surrounding the ducts and alveoli of the gland. Oxytocin also stimulates uterine contraction during labor to expel the fetus and placenta (1).
• Antidiuretic Hormone (ADH) or Vasopressin: produced in response to hypovolemia (or water depletion) to upregulate water reabsorption by the kidneys, subsequently maintaining proper blood volume and blood pressure.

How Does the Pituitary Gland Work With Other Organs and Glands? 

The hypothalamus and the pituitary gland form a closely integrated system known as the hypothalamic-pituitary axis (HPA). The hypothalamus produces several releasing and inhibiting hormones that act on the pituitary gland, stimulating the release of pituitary hormones (3). These pituitary hormones travel through the bloodstream to their target organs as part of a tightly regulated hormonal cascade involved in the maintenance of total body homeostasis. A negative feedback mechanism exists by which hormones released by the target glands affect the HPA and ensure that hormone blood levels are maintained within appropriate boundaries (6).

The anterior pituitary produces several important hormones that either stimulate target glands to produce hormones or directly affect target organs:

Adrenal Glands: ACTH stimulates the adrenal cortex to produce cortisol. Cortisol is involved in the stress response, immune function, and regulation of inflammation.

Gonads (Ovaries and Testes): FSH and LH stimulate the gonads to produce female and male sex hormones (estrogen and progesterone in females, testosterone in males). The sex hormones are essential for reproductive development and fertility.

Thyroid Gland: TSH stimulates the thyroid gland to produce thyroid hormones (T3 and T4). The thyroid hormones are vital in maintaining basal body temperature and regulation of metabolism.

Mammary Glands: Prolactin acts directly on the mammary glands to stimulate milk production in lactating women.

Bone, Skeletal Muscles, and Other Cells: GH plays a pivotal role in controlling the body’s growth and development (3).

Kidneys: ADH (or Vasopressin) released from the posterior pituitary, promotes the reabsorption of water from the kidneys to maintain adequate blood volume and blood pressure.

Oxytocin, the second hormone released from the posterior pituitary, stimulates the contractions of the Uterus during childbirth and activates milk ejection in response to suckling during breastfeeding (3).

Conditions Related to the Anterior Pituitary

Hyperpituitarism

Hyperpituitarism or pituitary hyperfunction is the overproduction of hormones by the pituitary glands. The causes of hyperpituitarism may include pituitary adenomas, hyperplasia, or carcinomas of the anterior pituitary. Conditions characterized by excessive secretion of hormones from the anterior pituitary are as follows:

Acromegaly and Gigantism: caused due to the excessive secretion of GH (and hepatic secretion of insulin-like growth factor 1; IGF-1), commonly caused by a GH-secreting pituitary adenoma (benign tumor). Gigantism (in children) and Acromegaly (in adults) occur before and after epiphyseal closure (1), respectively. Clinical presentation may include enlarged hands and feet, facial changes, congestive heart failure, carbohydrate intolerance, or diabetes.

Hyperprolactinemia: elevated levels of prolactin in the blood most commonly due to a prolactinoma. Excess prolactin inhibits the normal secretion of FSH and LH, leading to gonadal dysfunction including irregular menstruation, lack of ovulation, loss of libido, and infertility.

Secondary Hyperthyroidism: excessive production of TSH from the anterior lobe results in the overstimulation of the thyroid gland. Symptoms of hyperthyroidism may include weight loss, heart palpitations, tremors, heat insensitivity, and anxiety.

Cushing’s Disease: results from an ACTH-secreting pituitary adenoma (2). The overproduction of ACTH stimulates the adrenal cortex to overproduce cortisol resulting in obesity, hypertension, diabetes, and the classical clinical symptoms of the “moon face” or “buffalo hump” on the back of the neck.

Hypopituitarism  

Hypopituitarism conditions are associated with decreased secretion of pituitary hormones, which may originate from the hypothalamus or the pituitary gland. Hypofunction of the anterior pituitary occurs when approximately 75% of the parenchyma is lost or absent (4). Some common causes of anterior pituitary hypofunction include the following:

Pituitary Tumors and Mass Lesions: tumors may compress and exert pressure on the pituitary gland, thus impairing its function.

Traumatic Brain Injury and Subarachnoid Hemorrhage: damage to or disruption of the blood supply to the anterior pituitary may result in hypopituitarism.

Pituitary Surgery or Radiation: surgical excision of a pituitary adenoma or radiation therapy to the brain can damage the pituitary gland and impair hormone secretion.

Pituitary Apoplexy: an enlarged pituitary adenoma that acquires arterial blood supply directly from the pituitary gland resulting in hemorrhagic infarction, which will result in hypopituitarism.

Sheehan Syndrome: ischemic necrosis of the pituitary gland that commonly occurs during pregnancy. Clinically presents with failure to lactate during the postpartum period (2).

Diagnosing Anterior Pituitary Conditions

A comprehensive diagnosis of anterior pituitary conditions should include a complete clinical assessment, lab testing, and imaging studies. A thorough investigation into a hypo- or hyperfunctioning anterior lobe may isolate a deficiency or excess of hormone secretion, a pituitary adenoma, or other structural abnormalities affecting the gland.

Medical History and Physical Examination

A thorough medical history and physical examination are essential in identifying signs and symptoms that may be suggestive of an anterior pituitary disease. Clinical manifestations vary based on the specific hormone affected, however, common signs may include growth abnormalities, amenorrhea, infertility, and metabolic conditions such as diabetes.

Hormone Testing

Serum hormone levels of the predominant hormone in question can be measured to determine whether the condition originates from a hypofunctioning or hyperfunctioning of the pituitary gland.

Elevated levels of Growth Hormone (GH) by Access Med Labs can be used to identify a GH-secreting Pituitary Adenoma essential for diagnosing Gigantism or Acromegaly. The diagnosis of a GH-secreting adenoma also involves the measurement of Insulin-like Growth Factor 1 (IGF-1) by Access Med Labs. IGF-1 measurement is recommended for patients presenting with typical clinical manifestations of Acromegaly (5). In patients with elevated serum IGF-1, Oral Glucose Tolerance Testing (OGTT) is performed. In healthy patients, OGTT suppresses GH secretion. Hence, a lack of suppression of GH to <1 µg/L is used to confirm the biochemical diagnosis of acromegaly (5).

Prolactinomas are the most prevalent pituitary adenomas. If a patient is clinically presenting with symptoms of amenorrhea, galactorrhea, infertility, and hypogonadism, elevated levels of Prolactin by Access Med Labs can aid in the identification of a Prolactinoma. A Prolactinoma may lead to hyperprolactinemia or have a mass effect and present with hypopituitarism due to compression of the pituitary stalk (5).

Cushing’s Disease due to an ACTH-secreting Pituitary Adenoma is characterized by hypercortisolism. Overproduction can be confirmed with ACTH by Access Med Labs or the DUTCH Complete (Dried Urine) and DUTCH Plus by Precision Analytical giving a complete overview of the hypothalamic-pituitary axis (HPA) dysfynction. The current guidelines recommend at least two urine or salivary cortisol measurements such as Diurnal Cortisol by Doctor's Data to validate results and improve test confidence (5).

Radiographic Imaging

Imaging modalities such as MRI and CT scans can be performed to visualize the presence of pituitary adenomas and other structural abnormalities or lesions affecting the gland.

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Key Takeaways

The pituitary gland, often referred to as the “master gland”, plays a central role in regulating vital physiological processes throughout our body by secreting hormones.

• The pituitary gland has two anatomically and functionally distinct regions: the anterior pituitary lobe (or the adenohypophysis) and the posterior pituitary lobe (or the neurohypophysis).
• The pituitary gland is tightly regulated by releasing and inhibiting hormones produced by the hypothalamus.
• The anterior pituitary synthesizes and secretes several hormones: Growth Hormone (GH), Prolactin, Adrenocorticotropic Hormone (ACTH), Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), and Thyroid-stimulating Hormone (TSH).
• Anterior pituitary hormone secretion is controlled by a negative feedback loop involving the target organs.
• Damage or dysfunction to the anterior pituitary can lead to various hypo- and hyperfunctioning endocrine disorders, for example, Acromegaly (excess GH), Prolactinoma (excess Prolactin), and Cushing’s Disease (excess ACTH).
• The diagnosis of conditions associated with the pituitary gland involves a comprehensive clinical assessment, measurement of serum or urine hormone levels, and imaging studies.