Pituitary Gland

The pituitary gland, often referred to as the "master gland," is a small, pea-sized organ located at the base of the brain, just below the hypothalamus. It plays a critical role in regulating various bodily functions by secreting hormones that control other glands in the endocrine system, such as the thyroid, adrenal glands, and reproductive organs. 

1.0Introduction

• Origin: Based on development, the pituitary gland is completely ectodermal. 
• Location: It is located in the bony cavity of a sphenoid bone known as sella turcica. 
• This gland is attached to the hypothalamus through a stalk called an infundibulum. 
• It is divided anatomically into an adenohypophysis (anterior pituitary) and a neurohypophysis (posterior pituitary).

2.0Anatomical structure of the Pituitary Gland  

• The embryonic development of the lobes of the pituitary gland is entirely distinct. 
• The anterior lobe is derived from an inward invagination of the primitive mouth cavity (oral ectoderm) known as Rathke's pouch. In contrast, the neural lobe arises from the neural ectoderm of the floor of the developing forebrain, the infundibulum of the diencephalon. Cells of the anterior wall of Rathke's pouch develop into the pars distalis, containing most of the hormone-producing cells of the adenohypophysis.
• The pituitary gland has three parts: the adenohypophysis (alternatively referred to as the anterior lobe or the Pars Distalis), the intermediate lobe (or Pars Intermedia), and the neurohypophysis (also called the posterior lobe or Pars Nervosa). 
• The adenohypophysis is primarily glandular tissue that receives hormones through the hypothalamic hypophyseal portal system, while the neurohypophysis consists of nerve inputs that originate from the soma of neurosecretory neurons in supraoptic and paraventricular nuclei  of the hypothalamus. 
• These nerve endings travel through the continuous median eminence with the infundibulum, or pituitary stalk, and ultimately release the hormones in the posterior lobe. 

Anatomical structure of the Anterior Pituitary Gland 

• The anterior pituitary gland is composed of various cell types secretes several hormones: corticotrophs (adrenocorticotropic hormone; ACTH), somatotropes (growth hormone; G.H.), lactotropes (prolactin; P.R.L.), gonadotropes (luteinizing hormone; L.H., and follicle-stimulating hormone; F.S.H.) and thyrotropes (thyroid-stimulating hormone; TSH). 
• The anterior lobe of the pituitary extends dorsally to form a non-secretory tissue that wraps around the infundibular stalk known as Pars Tuberalis.
• An intermediate lobe develops between the two lobes and can vary greatly in size among different species; in humans, this regresses and disappears in adults. In many vertebrates, the intermediate lobe produces hormones that include melanotropins, such as melanocyte-stimulating hormone (M.S.H.).

Anatomical Structure of the Posterior Pituitary

• The posterior pituitary primarily consists of neural tissue, which receives input from the axons of neurosecretory cells present in supraoptic and paraventricular nuclei of the hypothalamus. 
• The axons traverse the hypothalamo-hypophyseal tract and terminate blood capillaries in the posterior pituitory, where hormones are released which are then stored in the posterior pituitary gland.
• These neurons produce two hormones vasopressin and oxytocin. 
• Posterior pituitary gland does not synthesize any hormone ,it only stores and releases hormones.

Specific Antibodies 

Specific antibodies against the pituitary hormones identify five cell types:

• Somatotrophs, producing growth hormone (GH): These acidophilic cells constitute half of all the hormone-producing cells in the anterior pituitary. 
• Lactotrophs (mammotrophs), producing prolactin: These acidophilic cells secrete prolactin, which is essential for lactation. 
• Corticotrophs: These basophilic cells produce adrenocorticotropic hormone (ACTH), pro-opiomelanocortin (POMC), melanocyte-stimulating hormone (MSH), endorphins, and lipotropin. 
• Thyrotrophs: These pale basophilic cells produce thyroid-stimulating hormone (TSH). Gonadotrophs: These basophilic cells produce both follicle-stimulating hormone (FSH) and luteinizing hormone (LH). FSH stimulates the formation of graafian follicles in the ovary, and LH induces ovulation and the formation of corpora lutea in the ovary. The same two hormones also regulate spermatogenesis and testosterone production in males.

3.0Hormones Secreted by Adenohypophysis

Growth Hormone 

Growth Hormone or Somatotropic Hormone [G.H. or S.T.H]

Effect on growth:

• Promotes elongation of bones 
• G.H. promotes mitosis & increases the number of cells in many visceral organs, e.g. liver 
• G.H. stimulates the growth of muscle and cartilage
• Effect on metabolism Fat : Enhances lipolysis. Growth hormone promotes the use of fat as an energy source over carbohydrates and proteins.
• Carbohydrate: G.H. decreases glucose uptake in the cells, also called the diabetogenic hormone. 
• Diabetogenic effect of GH: Hypersecretion of GH increases blood glucose level enormously. It causes continuous stimulation of the β-cells in the islets of Langerhans in pancreas and increase in secretion of insulin. In addition to this, the GH also stimulates β-cells directly and causes secretion of insulin. Because of the excess stimulation, β-cells are burnt out at one stage. This causes deficiency of insulin, leading to true diabetes mellitus or full-blown diabetes mellitus. This effect of GH is called the diabetogenic effect.
• Protein: G.H. increases amino acid uptake by the cells of the liver & muscles & helps in protein synthesis. 

Diseases Due to Hyposecretion 

Diseases due to hyposecretion or hypersecretion of Somatotropin hormone

(a) Hyposecretion of STH 

• Due to a deficiency of STH in childhood or adolescence, pituitary dwarfism is observed. 
• Dwarfism is caused by the defect of the pituitary, which is called ateliosis. 
• Clowns of the circus are such dwarfs that they are called midgets. 
• Intelligence and alertness are normal, but sexual maturation is delayed. 
• If a deficiency of E.H. occurs after puberty, then it causes acromicria.

(b) Hypersecretion of STH 

• Due to the hypersecretion of G.H. in childhood, the bones of the legs and hands become very long, and the person's height increases greatly. The body becomes imbalanced. This disease is called Gigantism. 
• Excessive secretion of growth hormone in adults, particularly during middle age, can lead to a condition known as acromegaly. This condition is characterized by significant enlargement of the bones in the face, spine, and extremities, resulting in severe physical changes. If left untreated, acromegaly can cause serious complications and may lead to premature death.

(i) Prolactin / Lactotrophic Hormone (PRL/LTH)  

• Regulates the growth of mammary glands and the formation of milk. 
• Responsible for lactation after delivery. 
• Hormone of maternity.

(ii) Adrenocorticotropic Hormone (ACTH) 

• Stimulates the synthesis and secretion of steroid hormones from the adrenal cortex. (Mainly Glucocorticoids)

(iii) Thyrotrophic [T.T.H OR T.S.H.] or Thyroid Stimulating Hormone 

• T.S.H. stimulates the thyroid gland to secrete thyroxine. 
• TSH helps in almost all steps of thyroid hormone synthesis & it causes the growth of the thyroid gland. 
• The Thyrotropin factor of the hypothalamus stimulates the secretion of TSH.

(iv) Follicle Stimulating Hormone [FSH] 

• It is secreted in males and females. 
• In males, it stimulates spermatogenesis and the normal functioning of seminiferous tubules. 
• In females, it stimulates the oogenesis and development of Graafian follicles in the ovary. 
• Estrogen hormone that is secreted by Graafian follicles is also affected by F.S.H.

(v) Luteinizing Hormone [LH Or ICSH] or Interstitial Cell Stimulating Hormone 

• It stimulates ovulation in females. As a result of this, corpus luteum is formed. 
• The hormone progesterone, secreted by the corpus luteum, is also stimulated by L.H. 
• In men, L.H. is called ICSH. It affects the Leydig cells or Interstitial cells of the testes and stimulates the secretion of the male hormone Testosterone. 
• F.S.H. and L.H. are both called gonadotrophic hormone GTH. 
• F.S.H. and L.H. act in combined form, which are called synergistic hormones.
• Gonadotrophic hormones (F.S.H. & L.H.) secretion starts during puberty. The hypothalamus regulates their secretion.

(vi)Melanocyte Stimulating Hormone (MSH) / Intermedin)

• Target organ  -Skin 
• Functions—It Regulates skin pigmentation (Darkening) and is responsible for color change in Amphibians and Reptiles (Metachrosis). M.S.H. is functional in Poikilotherms.

4.0Hormones Secreted by Neurohypophysis

(i) Oxytocin or Pitocin or Birth Hormone 

• Oxytocin influences the smooth muscles in our body, promoting their contraction. 
• In females, it plays a crucial role during childbirth by inducing strong contractions of the uterus and facilitating milk ejection from the mammary glands. 
• It is considered the primary hormone involved in labor and delivery.
• It stimulates the fast/ rapid contractions and expansions of non-striated muscles of the uterine wall at the last moment of the gestation period (pregnancy). Due to these uterine contractions, labor pains start just before childbirth.  
• This hormone is secreted by the mother's pituitary gland at the time of parturition. 
• Oxytocin hormone contracts the myoepithelial cells on all sides of the alveoli of mammary glands. Thus, it helps in milk ejection and is also called the milk-letting hormone. 
• This hormone is related to emotion in females. Even the cry or sound of a baby can release this hormone in a lactating mother.

(ii) ADH or Vasopressin or Pitressin 

• It acts mainly in the kidney and stimulates the reabsorption of water and electrolytes by the distal convoluted tubules (in D.C.T. and collecting duct of nephrons), thereby reducing the loss of H2O through urine (Diuresis). Hence, it is also called "Antidiuretic hormone (ADH)".
• Hyposecretion of ADH causes "Diabetes insipidus" (taste less urine or water drinker's disease), which is characterized by polyuria, diluted urine, dehydration, excessive thirst (polydipsia), low B.P. (hypotension), etc. 
• Intake of coffee, tea, excess alcohol, etc., decreases ADH secretion. 

5.0Pituitary Tumors /Adenomas

CAUSES:

• The most common cause of hyperpituitarism is an adenoma arising in the anterior lobe. 
•  Some pituitary adenomas can secrete two hormones (GH and prolactin being the most common combination), and rarely, pituitary adenomas are plurihormonal.
•  Pituitary adenomas can be functional (i.e., associated with hormone excess and clinical manifestations thereof) or nonfunctioning (without clinical symptoms of hormone excess). 
• Less common causes of hyperpituitarism include pituitary carcinomas and some hypothalamic disorders.
•  Large pituitary adenomas, and particularly nonfunctioning ones, may cause hypopituitarism as they encroach on and destroy adjacent anterior pituitary parenchyma.
• Pituitary adenomas are usually found in adults, with a peak incidence from 35 to 60 years of age. They are designated, somewhat arbitrarily, microadenomas if they are less than 1 cm in diameter and macroadenomas if they exceed 1 cm in diameter.

SYMPTOMS:

• The signs and symptoms of pituitary adenomas include endocrine abnormalities and mass effects. The effects of excessive secretion of anterior pituitary hormones are mentioned below, when the specific types of pituitary adenoma are described. Briefly, these include 
• radiographic abnormalities of the sella turcica
•  visual field abnormalities
•  signs and symptoms of elevated intracranial pressure
• occasionally hypopituitarism 
• Acute hemorrhage into an adenoma is sometimes associated with pituitary apoplexy.
• Benign tumors that can affect hormone production .
• As Pituitary tumor or diffuse enlargement proceeds, it pushes up on the optic chiasma from below, producing a bitemporal hemianopsia first manifested in the upper quadrants, often to a blinking or flashing red light.
•  This finding is too subtle for the generalist's confidence, however, and pituitary assessment depends on formal visual fields and imaging. 

6.0Types of Adenoma with their associated Symptoms

Prolactinomas:

• Prolactinomas (lactotroph adenomas) are the most frequent type of hyperfunctioning pituitary adenoma, accounting for about 30% of all clinically recognized cases.
•  These lesions range from small microadenomas to large, expansile tumors associated with substantial mass effect. Prolactinomas have a propensity to undergo dystrophic calcification, ranging from isolated psammoma bodies to extensive calcification of virtually the entire tumor mass (“pituitary stone”)
• Prolactin secretion by functioning adenomas is usually efficient and proportional, in that serum prolactin concentrations tend to correlate with the size of the adenoma. 
• Increased serum levels of prolactin, or prolactinemia, cause amenorrhea, galactorrhea, loss of libido, and infertility. Hyperprolactinemia may result from causes other than prolactin-secreting pituitary adenomas . 

Growth Hormone Cell (Somatotroph) Adenomas:

• GH-secreting tumors are the second most common type of functioning pituitary adenoma. Somatotroph cell adenomas may be quite large by the time they come to clinical attention because the manifestations of excessive GH may be subtle. 
• Persistently elevated levels of GH stimulate the hepatic secretion of insulin-like growth factor 1 (IGF-1 or somatomedin C), which causes many of the clinical manifestations.
•  If a somatotropic adenoma appears in children before the epiphyses have closed, the elevated levels of GH (and IGF-1) result in gigantism. This is characterized by a generalized increase in body size with disproportionately long arms and legs. 
• If the increased levels of GH are present after closure of the epiphyses, patients develop acromegaly. In this condition, growth is most conspicuous in skin and soft tissues; viscera (thyroid, heart, liver, and adrenals); and bones of the face, hands, and feet. Bone density may be increased (hyperostosis) in both the spine and the hips. Enlargement of the jaw results in protrusion (prognathism), with broadening of the lower face. The hands and feet are enlarged with broad, sausage-like fingers.
•  In most instances gigantism is also accompanied by evidence of acromegaly. These changes develop for decades before being recognized, hence the opportunity for the adenomas to reach substantial size. GH excess is also correlated with a variety of other disturbances, including gonadal dysfunction, diabetes mellitus, generalized muscle weakness, hypertension, arthritis, congestive heart failure, and an increased risk of gastrointestinal cancers.
• The underlying pituitary adenoma can be either removed surgically or treated via pharmacologic means.

Acth Cell (Corticotroph) Adenomas:

•  Corticotroph adenomas are usually small microadenomas at the time of diagnosis. Excess production of ACTH by the corticotroph adenoma leads to adrenal hypersecretion of cortisol and the development of hypercortisolism (also known as Cushing syndrome).
• When the hypercortisolism is due to excessive production of ACTH by the pituitary, the process is designated Cushing disease. Large destructive adenomas can develop in patients after surgical removal of the adrenal glands for treatment of Cushing syndrome. This condition, known as Nelson syndrome, occurs most often because of a loss of the inhibitory effect of adrenal corticosteroids on a preexisting corticotroph microadenoma. Because the adrenals are absent in persons with this disorder, hypercortisolism does not develop.
•  In contrast, patients present with mass effects of the pituitary tumor. In addition, there can be hyperpigmentation because of the stimulatory effect of other products of the ACTH precursor molecule on Pituitary Adenomas & Hyperpituitarism  melanocytes.

Other Anterior Pituitary Adenomas

Gonadotroph (LH-producing and FSH-producing) adenomas 

• It can be difficult to recognize because they secrete hormones inefficiently and variably, and the secretory products usually do not cause a recognizable clinical syndrome (non-functioning adenomas). 
• Gonadotroph adenomas are most frequently found in middle-aged men and women when they become large enough to cause neurologic symptoms, such as impaired vision, headaches, diplopia, or pituitary apoplexy.
•  Pituitary hormone deficiencies can also be found, most commonly impaired secretion of LH. This causes decreased energy and libido in men (due to reduced testosterone) and amenorrhea in premenopausal women. Thus, gonadotroph adenomas are paradoxically associated with secondary gonadal hypofunction. 

Thyrotroph (TSH-producing) adenomas are rare, accounting for approximately 1% of all pituitary adenomas. Thyrotroph adenomas are a rare cause of hyperthyroidism. 

Nonfunctioning pituitary adenomas are a heterogeneous group that constitutes approximately 25% to 30% of all pituitary tumors.. In the past, many such tumors have been called silent variants or null-cell adenomas. Not surprisingly, the typical presentation of non functioning adenomas is mass effects. These lesions may also compromise the residual anterior pituitary sufficiently to cause hypopituitarism. This may occur as a result of gradual enlargement of the adenoma or after abrupt enlargement of the tumor because of acute hemorrhage (pituitary apoplexy).

Pituitary carcinomas are quite rare, accounting for less than 1% of pituitary tumors. The majority of pituitary carcinomas are functional neoplasms, with prolactin and ACTH being the most common secreted products. Metastasis usually appears late in the course, following multiple local recurrences.