The Human Body Quiz - Pituitary Gland

T3 suppression test:

Large doses of T3 given – negative feedback to hypothalamus & anterior pituitary – normal: TSH suppressed.

If TSH not suppressed: Tumour (autonomous)

All manifests, but the most evident manifestation is Medullary carcinoma of thyroid.

Other causes of hypersecretion besides MEN:

1. Carney Complex

* Autosomal dominant disorder
* Characterized often by cardiac, endocrine, cutanueous, breast & skin spotty pigmentation.
* Tumour

In hyperglycemic state -> GH is inhibited.

Receptor tyrosine kinases are a type of cell surface receptor that, when activated by binding to a specific ligand, have the ability to phosphorylate intracellular mediators. This phosphorylation event then triggers a cascade of signaling events within the cell, ultimately leading to a specific cellular response. Therefore, receptor tyrosine kinases act as protein kinases by phosphorylating intracellular mediators to produce action.

Tyrosine kinase is a protein kinase. The hormones that bind to this receptor are: Insulin, GH, PRL, Oxytocin, Erythropoietin, Growth factors

Prolactin is not a tropic hormone because it does not act on a target endocrine gland to promote hormone secretion. Instead, it acts on the mammary glands in the breasts to stimulate milk production. Tropic hormones, such as thyroid hormone, LH, GH, and FSH, target specific endocrine glands to regulate the secretion of hormones from those glands.

A pituitary tumor is best described as a neoplasm located in the sella turcica. The sella turcica is a bony structure in the skull where the pituitary gland is located. A neoplasm refers to an abnormal growth of cells, which can be benign or malignant. In the case of a pituitary tumor, it is typically a benign growth of cells in the pituitary gland. Therefore, the best description of a pituitary tumor is a neoplasm located in the sella turcica.

Observe the 2nd graph, the black arrow indicates when the DDAVP is administered. Upon administration, patient with CDI (Cranial) urine osmolality increases. Whereas, NDI (nephrogenic) the osmolality remains low.

IF given TRH injection, TSH normal: Hypothalamic defect. If TSH remain low: Pituitary defect.

* Wermer’s syndrome
* Manifestation:
o Hyperparathyroidism *
o Pancreatic tumours
o Pituitary adenoma
o Carcinoid tumours
o Adrenal adenomas
o Subcutaneous lipomas
o Facial angiofibromas
o Collagenomas
* Less than 1% of pituitary tumours
* Gene mutations: menin
* Screen for ZES. If positive, screen for MEN1

Cushing's disease is a condition characterized by excessive production of cortisol, a hormone that helps regulate various bodily functions. Therefore, the correct answer is cortisol deficiency, as Cushing's disease is the opposite of this condition.

Sipple's syndrome is the correct answer for the question. MEN type 2A, also known as Sipple's syndrome, is a hereditary condition characterized by the development of medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. It is caused by mutations in the RET proto-oncogene. Cushing's syndrome is a condition caused by prolonged exposure to high levels of cortisol, Wermer's syndrome is associated with multiple endocrine neoplasia type 1, and Nelson's syndrome is a disorder that occurs following the removal of both adrenal glands.

The rest are features of the chromophils.

The Pars Anterior consists of cords & clump of endocrine cells (secrete hormone into blood) and large capillary sinusoids (blood). In the pars anterior itself has 2 types of cells,

1. Chromophils (phil: like to take up stains): Secretory

* Acidophils: Secrete growth hormones & prolactin
* Basophils: Secrete TSH, ACTH, LH, FSH, ICSH (stimulating hormones that act on other endocrine organs to secrete their respective hormones).

2. Chromophobes (phobe: dont like to take up stains): not secretory

Prolactinoma: Give dopamine agonist (inhibits prolactin). Reduces hyperprolactinemia, reduce tumour size.

When the hormone binds to the receptor (ligand interaction), the receptor will undergo conformational changes (change shape), which activates G-protein in the cell (which can be stimulatory, Gs, or inhibitory, Gi). Assuming that it is stimulatory, it will cause phosphorylation of GDP to convert to GTP which will bind to the effector (enzyme adenylyl cyclase) coverting ATP to cAMP. cAMP will activate Protein Kinase A which inturn will lead to phosphorylation of intracellular mediators called second messengers (relay message from the hormone) producing intracellular effects.

In the case of maternal iodine deficiency, it can lead to neonatal hypothyroidism or cretinism in the child. Cretinism is easily treatable by providing the child with TSH. If the level of T4 remains low, the appropriate treatment for the child would be to administer T4. This is because T4 is the main thyroid hormone responsible for regulating metabolism and growth in the body. By providing the child with T4, it helps to restore the normal levels of thyroid hormone in the body and alleviate the symptoms of hypothyroidism.

GH-deficient dwarfs: Eventhough it responds to GH normally, but there is no GH. No GH, no IGF-1. Even in hypoglycemia, GH levels will fail to increase.

Pygmies: They lack IGF-1 eventhough there is normal GH. This is because IGF-1 is not produced when GH binds to GH receptor. Therefore, there is no growth. They have a post-GH receptor defect.

Laron type dwarfs: They have high amounts of GH, but it cannot bind to the GH receptor. They lack functional hepatic GH receptors.

Therefore, pygmies & Laron type dwarfs are due to target organ resistance.

GH-deficient dwarfs: Eventhough it responds to GH normally, but there is no GH. No GH, no IGF-1. Even in hypoglycemia, GH levels will fail to increase.

Pygmies: They lack IGF-1 eventhough there is normal GH. This is because IGF-1 is not produced when GH binds to GH receptor. Therefore, there is no growth. They have a post-GH receptor defect.

Laron type dwarfs: They have high amounts of GH, but it cannot bind to the GH receptor. They lack functional hepatic GH receptors.

Therefore, pygmies & Laron type dwarfs are due to target organ resistance.

Oculomotor is located most medially

During the last few hours before waking up, ACTH (adrenocorticotropic hormone) and cortisol levels are high. This is because the body naturally produces higher levels of these hormones in the early morning to help wake up and prepare for the day ahead. The increase in ACTH stimulates the release of cortisol from the adrenal glands, which helps regulate metabolism, blood pressure, and the body's response to stress.

The parvocellular neurosecretory neurons project into the median eminence before releasing peptides into the blood vessels. The median eminence is a part of the hypothalamus located at the base of the brain. It serves as a gateway for the release of hormones into the bloodstream. The peptides released by the parvocellular neurosecretory neurons stimulate the synthesis and secretion of hormones from the anterior pituitary gland.

The clinical features of prolactinoma include amenorrhea (absence of menstrual periods), galactorrhea (abnormal milk production), loss of libido (decreased sexual desire), and infertility (inability to conceive). These symptoms are caused by the excess production of prolactin, a hormone that regulates reproductive function. Amenorrhea occurs because high levels of prolactin disrupt the normal menstrual cycle. Galactorrhea is the result of prolactin stimulating milk production in the breasts. Loss of libido and infertility can occur due to hormonal imbalances caused by prolactinoma.

The correct answer is total thyroidectomy with central lymph node dissection. MEN type 2B is a hereditary condition that causes the development of multiple neuromas, including those on the lips and tongue. These neuromas are associated with the presence of medullary thyroid carcinoma (MTC), a type of thyroid cancer. The treatment for MEN type 2B involves the complete removal of the thyroid gland (total thyroidectomy) along with the removal of the central lymph nodes (central lymph node dissection). This is done to prevent the progression of MTC and reduce the risk of metastasis.

* Pulse: Rhythmical dilation of an artery, produced by the increased volume of blood into the vessel by the contraction of the heart.
* Pulse rate: Frequency of the arterial pulsation palpated per minute

Growth hormone affects various aspects of growth in the body. It promotes cartilage growth, which is essential for the development and maintenance of bones and joints. It also stimulates linear and width bone growth, contributing to overall skeletal growth and development. Additionally, growth hormone plays a role in organ growth, ensuring proper development and functioning of organs. Lastly, it stimulates muscle growth, aiding in the increase of muscle mass and strength.

Demeclocycline: V2 receptor antagonist. interferes with cAMP production, reverse antidiuresis effect

Defect to the thirst mechanism located in the anterior hypothalamus, results in an abnormal increase in thirst & fluid intake that suppresses ADH & increase urine output. Desmopressin/DDAVP is ineffective --- will lead to fluid overload if thirst remains.

The correct answer is 200ml because this is the amount of urine in the urinary bladder that distends and activates the stretch receptors, initiating the micturition reflex. When the bladder reaches this level of distension, it sends signals to the brain to initiate the urge to urinate.

IGF (Insulin-like Growth Factor) was known as a 'sulfation factor' because it incorporates sulphate into cartilage. This means that IGF plays a role in the process of adding sulphate molecules to cartilage, which is important for the growth and maintenance of cartilage tissue.

Acral bone growth refers to the enlargement of bones in the extremities, such as the hands and feet. This is a characteristic symptom of acromegaly, which is caused by the hypersecretion of growth hormone in adults. In addition to acral bone growth, other common features of acromegaly include a protruding jaw, a larger skull, and enlarged hands and feet. These changes occur after the epiphyseal plate closes, which means that there is no further growth in long bones.

Occurs during pregnancy, woman produce vasopressinase in the placenta which breakdowns vasopressin. Can be treated with DDAVP. Some diseases of pregnancy activates hepatic vasopressinase (pre-ecclapsia, acute fatty liver etc.)

Prolactinemia is a side effect of a compressed pituitary stalk. The pituitary gland plays a crucial role in regulating hormone levels in the body, including the hormone prolactin. When the pituitary stalk is compressed, it can disrupt the normal functioning of the pituitary gland, leading to an increase in prolactin levels. This condition is known as prolactinemia. Prolactinemia can cause various symptoms such as irregular menstrual periods, breast milk production in non-pregnant women, and decreased libido in both men and women.

Nelson syndrome
-Largely destructive adenoma develop after surgical removal of adrenal glands
-Hyperpigmentation (MSH)
-Mass effect
-No hypercortisolism

Due to hyperplasia of the lactotroph (secrete prolactin). It can be caused by:

1) Interference with dopamine inhibition (no inhibition of lactotroph)
2) Damage to dopanergic neurons of hypothalamus from trauma (no dopamine)
3) Mass in suprasellar compartment : Stalk effect

* Antidiuresis
* Water reabsorption
* Concentrated urine (inappropriately high urine osmolality)
* Diluted plasma (low plasma osmolality)
* Dilutional water expansion (ECF > 10%) inhibit aldosterone secretion
* Increase renal excretion of NA+ (SALT WASTING) –> Hyponatraemia.

For water to be actively reabsorbed, Na+ will be exchanged with H20, and enter into the tubules to be excreted.

(RECHECK)

* Dry mouth
* Loss of skin turgor
* Sunken eyes
* Reduced BP varying with posture (Systolic * Increase pulse rate (>90/minute)

It is an epithelial tumours (stratified squamous cell epithelia). It represents a bimodal distribution (5-15 years old & 50 years above). Histologically: 3-4cm, encapsulated, cystic/ solid.

1. Adamantinomatous

Stratified squamous epithelium
Loose reticulum
Compact lamellar keratin (wet keratin)
Calcification
Chronic inflammation
Cholesterol rich yellowish fluid – machinery oil fluid

2. Papillary

Solid & papillary sheets of squamous epithelium
No keratin
No calcification
No cysts
No reticulum

the rest are actions of oxytocin

MEN 2B: Multiple neuromas on the lips & tongue. Marfanoid facies (look like a Marfan syndrome patient)

# Somatostatin analogues (reduce GH & IGF-1)
# Dopamine agonist (therapy for acromegaly, shrink tumour)
# Growth Hormone antagonist (Pegvisomant, bind to GH receptor & prevent dimerization)

The complication of SIADH is oedema formation and hypertension. SIADH, or Syndrome of Inappropriate Antidiuretic Hormone secretion, is a condition where the body produces too much antidiuretic hormone, leading to water retention and dilutional hyponatremia. The excessive water retention can cause fluid to accumulate in the tissues, leading to oedema formation. Additionally, the increased fluid volume can also lead to increased blood pressure, resulting in hypertension.

Oxytocin is a hormone that is produced in the hypothalamus and released by the pituitary gland. It has several actions in the body, including uterine contraction, which helps during labor and childbirth. It also assists in parturition, or the process of giving birth. Oxytocin is also responsible for milk ejection, or the release of breast milk from the mammary glands. Additionally, oxytocin plays a role in sperm transport during ejaculation.

* Pulse: Rhythmical dilation of an artery, produced by the increased volume of blood into the vessel by the contraction of the heart.
* Pulse rate: Frequency of the arterial pulsation palpated per minute

Therefore, ACTH have MSH activity as well (hyperpigmentation in excess, pallow in deficiency)

Trans-sphenoidal surgery is indicated in pituitary tumours when there is a progressive mass effect, which can cause symptoms such as visual loss and headache. It is also indicated in cases of hypersecretory disorders such as Cushing's syndrome, acromegaly, and hyperthyroidism, where the tumour is causing excessive hormone production. Additionally, trans-sphenoidal surgery may be necessary in cases of massive acute haemorrhagic necrosis of an adenoma, also known as pituitary apoplexy or Sheehan's syndrome.

Oxytocin and LH both have a positive feedback mechanism. Oxytocin is released during childbirth, stimulating contractions which in turn release more oxytocin, leading to stronger contractions. LH is involved in the menstrual cycle, where it stimulates the release of an egg from the ovary. This increase in LH triggers the release of more LH, creating a positive feedback loop. FSH and ADH do not have a positive feedback mechanism.

Protein synthesis: resembles actions of insulin

Carbohydrate metabolism: Oppose effect of insulin -> prolonged administration of GH will result in diabetes mellitus

Lipid metabolism: GH favours usage of FA as fuel. Therefore, glucose remains high/conserved.

Mineral metabolisme

Promotes positive Calcium, Magnesium & Phosphate balance.

Bone growth:

* Promotes growth of long bones at epiphyseal plates in growing children.
* Promotes appositional/ acral growth in adults.

Causes retention of Na+, K+ & Cl-

Prolactin-like effect

Due to it’s similar structure, it can bind to lactogenic receptors. Causes stimulation of mammary gland (lactogenesis).

hyperglycemia inhibits growth hormone secretion

During the first few hours of deep sleep, growth hormone (GH) is high in amount. This is because GH secretion is known to be highest during the early stages of deep sleep. Additionally, during strenuous exercise, GH levels also increase. Both deep sleep and strenuous exercise stimulate the release of GH, which plays a crucial role in growth and repair of tissues in the body.

1) Excessive hormone

* If it’s a funtioning tumour: high hormone level
* Non-functioning tumour: normal hormone level

2) Mass effect

* Intracranial mass: headache
* Loss of normal anterior pituitary hormone production due to compression
* Visual field defect: compression of optic chiasma (tunnel vision)
* Mild hyperprolactinemia (**stalk effect)

Increased plasma osmolality will stimulate release of ADH. Alcohol inhibits ADH secretion.

The complications of gamma knife radiation include hypopituitarism, glioma (tumor of glial cells), and sarcoma (malignant cancer of connective tissue).

ADH, also known as antidiuretic hormone or vasopressin, has multiple functions in addition to increasing water reabsorption in the distal nephron. It inhibits renin release, which helps regulate blood pressure by reducing the production of angiotensin II. ADH also increases vasoconstriction, narrowing the blood vessels and further contributing to blood pressure regulation. Additionally, it stimulates ACTH secretion from the anterior pituitary gland, working in synergy with CRH (corticotropin-releasing hormone) to regulate the release of cortisol. Finally, ADH promotes glycogenolysis in the liver, breaking down glycogen into glucose and increasing blood sugar levels.

# Manifestation 2B:

* Medullary carcinoma of thyroid
* Mucosal neuromas
* Marfanoid habitus (Marfan)
* Pheochromocytoma
* Ganglioneuromatosis of bowel

The given answer includes MEN, Carney complex, McCure-Albright Syndrome, and Neurofibrosis as causes of hypersecretion. MEN stands for Multiple Endocrine Neoplasia, which is a group of inherited disorders that cause overactivity and tumor formation in multiple endocrine glands. Carney complex is a rare genetic disorder that causes the formation of tumors in various parts of the body, including the endocrine glands. McCure-Albright Syndrome is a genetic disorder characterized by hormone overproduction and the presence of bone abnormalities. Neurofibrosis refers to the growth of tumors on nerves, which can lead to excessive secretion of certain hormones. These conditions can all result in hypersecretion of hormones.

Nicotine, Chlopropamide, and Morphine can induce a hypersecretion of vasopressin/ADH/AVP. Nicotine stimulates the release of ADH from the pituitary gland, leading to increased water reabsorption in the kidneys. Chlopropamide is a sulfonylurea drug that can cause ADH release by blocking the ATP-sensitive potassium channels in the hypothalamus. Morphine also stimulates the release of ADH, leading to increased water reabsorption. Therefore, all three drugs can cause SIADH by inducing a hypersecretion of vasopressin/ADH/AVP.

When GH binds to the dimeric receptor complex, it activates the JAK-2 protein, which leads to phosphorylation of the receptor and autophosphorylation of JAK-2 on tyrosine residues. This activation event triggers the activation of multiple signal pathways. The MAP kinase pathway is activated, which regulates gene transcription and protein activation. The PI 3 kinase pathway is also activated, which plays a role in cell survival and growth. Additionally, the activation of PLC leads to the production of diacylglycerol and the activation of protein kinase C, which are involved in various cellular processes.

* Monomorphic (just larger/more. No dysplasia)
* Uniform round cells
* Delicate stippled chromatin
* Inconspicuous nucleoli
* Moderate amounts of cytoplasm
* Mitoses: rare
* Ki67 labelling * Atypical variant

The pars distalis/anterior is a region of the pituitary gland that is composed of two types of cells: chromophils and chromophobes. Chromophils are hormone-secreting cells that can be further classified into acidophils and basophils based on the staining properties of their secretory granules. Acidophils secrete growth hormone and prolactin, while basophils secrete adrenocorticotropic hormone, thyroid-stimulating hormone, and follicle-stimulating hormone. On the other hand, chromophobes are non-secretory cells that appear pale and do not stain well. They are believed to be degranulated chromophils or precursor cells.