Hypothalamic AND Pituitary Function PDF

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HYPOTHALAMIC AND PITUITARY FUNCTIONPituitary Gland - Also known as HYPOPHYSIS. - “Master Gland” because the pituitary gland is the one who directly communicates with organs in distant sites such as thyroid, adrenal glands and pancreas.Hypothalamus - Portion of the brain located in the walls and floo...

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HYPOTHALAMIC AND PITUITARY FUNCTION Pituitary Gland - Also known as HYPOPHYSIS. - “Master Gland” because the pituitary gland is the one who directly communicates with organs in distant sites such as thyroid, adrenal glands and pancreas. Hypothalamus - Portion of the brain located in the walls and floor of the third ventricle. - The role of hypothalamus is the one who delivers the secretion of pituitary gland hormones; considered the link between nervous system and endocrine s

Embryology and Anatomy ● Anterior Pituitary Gland - Largest portion. - Also known as PARS DISTALIS/ ADENOHYPOPHYSIS. - Originated from Rathke’s pouch during the formation of diencephalon. ● Intermediate Bone - Poorly developed in humans and has little functional capacity. - Also known as PARS INTERMEDIA/ INTERMEDIALIS. ●

Posterior Pituitary Gland - Storage and release of oxytocin and vasopressin. - Also known as PARS NERVOSA/ NEUROHYPOPHYSIS. - Arise from diencephalon itself.

Pituitary functions can be detected during 7th to 9th weeks of gestation period.

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Sella Turcica - Space around pituitary gland. - Pocket of sphenoid where the pituitary resides.

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Infundibulum - Connects the anterior pituitary gland to the median eminence and hypothalamus. - Also known as PITUITARY STALK.

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Neurosecretory Tracts - Supraoptic-hypophyseal Tract, and Tuberohypophyseal Tract. - Connects the posterior pituitary gland to the supraoptic and paraventricular hypothalamic nuclei.

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Hypothalamic- Hypophyseal Portal System - Anterior pituitary gland receives 80- 90% of its blood supply and many hypothalamic factors.

Functional Aspects of the Hypothalamic- Hypophyseal Unit ● Open- Loop Negative Feedback Mechanism - Most endocrine feedback loops are of the open- loop variety. - It is subject or open for external modulation. ●

Pulsatility - All anterior pituitary hormones are secreted in a pulsatile fashion.

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Cyclicity - Many pituitary hormones are secreted in different amounts, depending on the time of day. - It has a circadian rhythm.

Hypothalamic Hormones Hormone

Action

Thyrotropin Releasing Hormone (TRH)

Release TSH and Prolactin.

Gonadotropin-Releasing Hormone (GnRH)

Release LH and FSH.

Corticotropin-Releasing Hormone (CRH)

Release ACTH.

Growth Hormone-Releasing Hormone (GHRH)

Release GH.

Somatostatin

Inhibits GH and TSH release (additional effects on gut and pancreatic function).

Dopamine (Prolactin Inhibitory Factor)

Inhibits prolactin release.

Prolactin Releasing Factors

Stimulates the release of prolactin.

Anterior Pituitary Cell Types Cells

Secretion

Lactotrophs

Prolactin

Somatotrophs

Growth Hormone

Thyrotrophs

TSH

Corticotrophs

ACTH

Gonadotrophs

LH and FSH

Anterior Pituitary Hormones ● Tropic Hormones - Actions are specific for another endocrine gland; the one who stimulates or communicates with another endocrine gland. LH

Men: Directs testosterone production from Leydig cells (testes). Women: Ovulation (ovary). It will order the corpus luteum of the ovary to produce progesterone.

FSH

Men: Spematogenesis. Women: Ovarian recruitment and early folliculogenesis; estrogen synthesis.

TSH

Thyroid hormone production.

ACTH

Regulates adrenal steroidogenesis; promotes glucocorticoid synthesis.

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Direct Effectors - Acts directly on tissue. ● GH- stimulates almost many types of tissues in the body. ● Prolactin- majority of its action is on the breast of women.

Growth Hormone - Produced by somatotrophs. - Release is stimulated by GHRH from hypothalamus. - Secreted in pulses (Average Pulse: 2- 3 hours ; Peak Secretion: Onset of Sleep). Actions of GH: ● Amphibolic hormone; it influences both anabolic and catabolic reactions. ● Effective transition from fed state to fasting state; without using substances when asleep. ● Antagonizes effects of insulin, because GH promotes gluconeogenesis and lipolysis, both of each increase in glucose level of blood. ● Stimulates production of Insulin-like Growth Factor 1 (IGF-1) and Somatomedin- C which is important in diagnosis.

Other Modifiers of Growth Hormone Secretion

STIMULATE GROWTH HORMONE SECRETION

INHIBIT GROWTH HORMONE SECRETION

Sleep

Glucose Loading

Exercise

Beta- Agonists (e.g., Epinephrine)

Physiologic Stress

Alpha- Blockers (e.g., Phentolamine)

Amino Acids (e.g., Arginine)

Emotional/ Psychogenic Stress

Hypoglycemia

Nutritional Deficiencies

Sex Steroids (e.g., Estradiol)

Insulin Deficiency

Alpha- Agonists (e.g., Norepinephrine)

Thyroxine Deficiency

Beta- Blockers (e.g., Propranolol) Growth Hormone- Lab Test ❖ Oral Glucose Testing ● Definitive test for GH production. ● Overnight fasting - 7 to 8 hours; maximum 12 hours. ● A drink of 100g oral glucose load, collect blood after 0 minute; after 1 hour, collect blood; after 1 hour again collect another blood. GH is measured at 0, 60, 120 minutes after glucose ingestion. Result Interpretation: ● GH is undetectable, it means normal. ● Increase in GH, it may be a sign of acromegaly. ❖ L-arginine Infusion ● Most widely used test for GH deficiency. ● Coupled with GHRH or L-DOPA; enzyme-coupled test. ● Normal Range: >3 - 5 ng/ mL. GH- Clinical Significance Acromegaly ● Pathologic or autonomous GH excess. ● Causes: ➔ Familial acromegaly; may be due to mutation in AIP gene. ➔ Sporadic cases; polymorphisms in SS receptor Type 5 gene. ● Gigantism - there is a growth hormone producing tumor that occurs before the epiphyseal closure during the fetal stage that will result in an impressive growth in height.

Acromegaly- Diagnosis ● Oral Glucose Loading Test - Definitive Test. ● IGF- 1 ( Somatomedin C) - Use to test patients with normal but inappropriate random levels of growth hormone. Acromegaly- Treatment ● Tumor Ablation (Invasive: Transsphenoidal Adenomectomy; Non-Invasive: Laser Therapy). ● GH Suppression ➔ SS analogs (octreotide, lanreotide). ➔ Dopaminergic agonists (cabergoline, bromocriptine). ➔ GH receptor antagonists (pegvisomant). GH Deficiency ● In Children - Familial (genetic defects) or tumor (craniopharyngiomas). - Structural lesions of pituitary or hypothalamus may cause GH deficiency. - Growth failure. ●

In Adults - Results of structural or functional abnormalities of pituitary.

Treatment ● GH replacement therapy. Prolactin ● Considered a stress hormone and has a vital role in relationship to reproduction. ● Physiologic Effect: Lactation Regulation: ● Tonic inhibition (dopamine). ● GnRH, TRH, and Vasoactive Intestinal Peptide.

Hyperprolactinemia ● A condition in which a person has higher-than-normal levels of the hormone prolactin in the blood. ● Hyperprolactinemia is due to: ➔ Medications- any compound that affects dopaminergic activity in median eminence; phenothiazine, reseigine, alpha-methyldopa. ➔ Disruptions of pituitary stalk, due to tumor, inflammation, and trauma. ➔ TRH and Estrogen- direct stimulation. ➔ Pathologic stimulation of neural suckling reflex, due to association with chest wall injuries during the ninth gestational period of the baby. ➔ Renal failure, PCOS. ➔ Physiologic stressors. ➔ Nursing (stimulation of breasts), it causes a release of prolactin stimulating hormone that stimulates through spinal reflex arc. Prolactinoma ● Pituitary tumor that directly secretes prolactin. ● Represents the most common type of functional pituitary tumor. Clinical Presentation: ● Premenopausal Women - Menstrual irregularity, infertility, galactorrhea. - Worst cases: Amenorrhea. ● Men and Post-menopausal Women - Symptoms of pituitary mass: headache or visual complaints. Clinical Evaluation of Hyperprolactinemia ● If pituitary tumor is suspected: - Careful assessment of anterior pituitary function (Lab Test/ Determination: Basal Cortisol, LH, FSH, and Androgen). - Evaluation of sellar anatomy with MRI. Other Causes of Hyperprolactinemia ● Substantial elevation in prolactin (>150 ng/mL), caused by prolactinoma. ● Modest elevation in prolactin (25 to 100 ng/mL), caused by infundibulum interruption and medication. Originally prolactin have two forms in bloodstream: ● 23-kD peptide- the principal and active form. ● 150-kD peptide- a big prolactin that has reduced biological potency. Macroprolactinemia ● When 150-kD peptide predominates. ● Asymptomatic.

How can you exclude the macroprolactinemia from hyperprolactinemia samples? ● Precipitate serum samples with polyethylene glycol (PEG) prior to measuring protein. Idiopathic Galactorrhea ● Increased lactation in women with normal prolactin levels. ● Seen in women who have been pregnant several times. ● Has no pathological implications. Hypopituitarism ● Loss of anterior pituitary function. ● Panhypopituitarism - Complete loss of pituitary function. ● Monotropic Hormone Deficiency - Loss of only single pituitary hormone. ● Etiology: - Pituitary hormone. - Sequelae of treatment of tumors. CAUSES OF HYPOPITUITARISM 1. Pituitary Tumors. 2. Parapituitary/ Hypothalamic Tumors 3. Trauma 4. Radiation Therapy/ Surgery 5. Infarction 6. Infection 7. Infiltrative Disease 8. Immunologic 9. Familial 10. Idiopathic Sheehan’s Syndrome ● Postpartum ischemic necrosis of pituitary following complicated delivery. ● Presents as unresponsive shock or failure to lactate. Lymphocytic Hypophysitis ● Autoimmune ● Ipilimumab

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Monoclonal antibodies that block cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). Associated with lymphocytic hypophysitis up to 5% of treated patients.

Posterior Pituitary Hormones ● Posterior Pituitary - Extension of the forebrain. - Storage region of vasopressin and oxytocin. - Both hormones are synthesized in the supraoptic and paraventricular nuclei of the hypothalamus. Oxytocin ● Cyclic nonapeptide; C-terminus is amidated. ● Has a critical role in lactation. ● Plays a major role in labor and parturition. ● Linked to maternal nurturing behavior and mother- infant bonding. ● Pitocin- synthetic oxytocin used to induce labor. Vasopressin - Major role in regulation of free water excretion. - Also a potent agent and affects blood clotting factors which will promote the release of factor VII and VWF. ● Receptors: - Vasopressin receptor in kidney (V2) - induces insertion of aquaporin 2 (water channel that transports water molecules in the tubular luminar membrane. ● Concentrated in collecting ducts. ● Coupled with adenylate cyclase. - Vasopressin receptors (V1a and V1b). ● Coupled with phospholipase C. ● Concentrated on factor VII and VWF secretion. ● Regulation - Hypothalamic Osmoreceptors ● Average osmotic threshold: 284 mOsm/kg. ● Plasma osmolality has a direct relationship with vasopressin secretion. - Vascular Baroreceptors ● Located in the left atrium, aortic arch, and carotid arteries. ● Initiate vasopressin release in response to a fall in blood volume or blood pressure (indirect relationship). ● 5 to 10% fall in arterial blood pressure will trigger vasopressin release. Diabetes Insipidus (DI) ● Consequence of vasopressin deficiency. ● Polyuria and polydipsia.

Diagnosis: ● Inappropriately low level of vasopressin with elevated plasma osmolality, ● Water Deprivation Test. ● Desmopressin (dDAVP) - synthetic analog to assess the patient’s response (neurogenic to central). Vasopressin Excess ● Leads to pathology retention of free water, restricting free water intake to mall amounts each day. Treatment: ● Vasopressin V2 antagonist. ❏ Conivaptan- euvolemic hyponatremia. ❏ Tolvaptan...