The Pituitary BMS200 (1).pdf

The Pituitary Gland BMS200 Dr. Melvia Agbeko, ND September 23 2024 Katlynn’s Story OUTCOMES Learning Outcomes Contrast the functional anatomy, hormone secretion, and regulation of hormone secretion in the anterior and posterior pituitary. Briefly describe the function of oxytocin and anti-d...

The Pituitary Gland BMS200 Dr. Melvia Agbeko, ND September 23 2024 Katlynn’s Story OUTCOMES Learning Outcomes Contrast the functional anatomy, hormone secretion, and regulation of hormone secretion in the anterior and posterior pituitary. Briefly describe the function of oxytocin and anti-diuretic hormone Describe the pathogenesis and relate to clinical features, and complications of common functional and non-functional pituitary growth and hypopituitarism. Briefly describe the functional anatomy and basic endocrinologic principles of the hypothalamic-pituitary- gonadal axis PRE-ASSESSMENT Quick Quiz Which of the following hormones is released from the posterior pituitary A. TS B. AD C. CR D. Somatostatin H H H ? Quick Quiz Prolactin is produced by which of the following cell type A. Thyrotrop B. Gonadotrop C. Lactotrop D. Somatotrope ? e e e PARTICIPATORY LEARNING Case Presentation Female patient (mid-20’s) presents with headache and some blurry vision, as well as amenorrhea and galactorrhea. Case Presentation Initial thoughts? What do you want to know/learn from this patient? Top 3-5 relevant hypotheses The Pituitary Gland  REVIEW: HPA – basic embryology The pituitary forms when two embryological regions grow towards each other and “meet ▪ Rathke pouch – outgrowth from the stomodeum that grows upwards towards the developing hypothalamus (part of diencephalon) Forms the anterior pituitar ▪ Infundibular process – inferior outgrowth from the developing hypothalamus Forms rest of the pituitary and infundibular stalk Rarely, a cyst (Rathke cleft cyst) or a tumour (craniopharyngioma) can develop from remnants of the Rathke pouch ” y REVIEW: Cranial anatomy – the hypophyseal fossa Note how the pituitary is almost completely surrounded by bone (sella turcica), and how close it is to the optic chiasm  REVIEW: HPA – basic functional divisions: Magnocellular neurons transport peptide hormones from the cell body (fast axonal transport) to their axon terminals in the posterior pituitar ▪ Released into the capillary plexus formed by the inferior hypophyseal arter ▪ Hormones from magnocellular neurons need to be released in adequate concentrations to impact tissues throughout the bod ▪ Major hypothalamic nuclei – PVN, SON y y y  HPA – basic functional divisions: Magnocellular neurons reside in (fairly) clearly-defined hypothalamic nucle ▪ PVN and SON (more later ▪ The PVN secretes mostly oxytocin, with a bit of AD ▪ The SON secretes mostly ADH, with a little oxytocin ) H i  Posterior pituitary – secreted hormones ADH (vasopressin, AVP) and oxytoci Small, 9-amino acid peptides that have a similar sequence and structur ADH is much more important in day-to-day maintenance of homeostasi ▪ The major regulator of water content in our bod ▪ Can also cause vasoconstrictio Oxytocin is a key hormone in the milk letdown reflex and in the augmentation of labour n s e n y Posterior Pituitary - overview Posterior Pituitary Physiology - ADH Two stimuli for release Osmoreceptors in the hypothalamus and in the lamina terminalis detect osmolarity of the extracellular fluid ▪ This is the major stimulus for ADH release ▪ in response to decreased osmolarity ! osmoreceptors shrink ! stimulate magnocellular neurons in the PVN/ SON ! ADH releas Baroreceptors (carotid sinus, aortic arch, or atria ▪ In response to decreased BP ! cells in the carotid sinus are stimulated ! communication with the PVN/ SON via the brainste ▪ Can also be stimulated by decreases in blood volume – as blood volume decreases ! less stretch at the atria ! release of ADH m e : )  Impact of osmolarity vs BP on ADH release Normal blood/ ECF osmolarity ranges from 275 – 295 mOsm As little as a 1% increase (3 mOsm) will result in secretion Pituitary Gland Overview 2 glands fused together Anterior- adenohypophysis endocrine epitheilial tissue Posterior- neurohypophysis neural tissue extension originating in the brain Relevant Anatomy Structure- lima-bean sized gland connected to the brain by an infundibulum Situated in the Sella Tursica (Sphenoid bone) 2 lobes- anterior and posterior Situated below both the Hypothalamus and the Optic Chiasm Secretion of hypothalamic hormones. The hormones of the posterior lobe (PL) are released into the general circulation from the endings of supraoptic and paraventricular neurons, whereas hypophysiotropic hormones are secreted into the portal hypophysial circulation from the endings of arcuate and other hypothalamic neurons. AL, anterior lobe; MB, mamillary bodies; OC, optic chiasm. Citation: Chapter 17 Hypothalamic Regulation of Hormonal Functions, Barrett KE, Barman SM, Brooks HL, Yuan JJ. Ganong's Review of Medical Physiology, 26e; 2019. Available at: https://accessmedicine.mhmedical.com/content.aspx?bookid=2525&sectionid=204292033 Accessed: August 29, 202 Copyright © 2023 McGraw-Hill Education. All rights reserved 3 Relevant Anatomy Vascular connection between Hypothalamus and Anterior Pituitary Neural connection between Hypothalamus and Posterior Pituitary Hypothalamic nuclei project axons into the posterior pituitary Supraoptic Paraventricular Innervation- Sympathetic/Parasympathetic Vascular Supply Hypophyseal portal system concentrated neurohormones are secreted into a capillary network and affect target organs through the blood supply Significance: smaller amounts can be secreted and have a potent effect Human hypothalamus, with a superimposed diagrammatic representation of the portal hypophysial vessels. Citation: Chapter 17 Hypothalamic Regulation of Hormonal Functions, Barrett KE, Barman SM, Brooks HL, Yuan JJ. Ganong's Review of Medical Physiology, 26e; 2019. Available at: https://accessmedicine.mhmedical.com/content.aspx?bookid=2525&sectionid=204292033 Accessed: August 29, 202 Copyright © 2023 McGraw-Hill Education. All rights reserved 3 Histology Embryonic origins Posterior Pituitary Evagination of the Third Ventricle Anterior Pituitary Rathke pouch- evagination of the roof of the pharynx Diagrammatic outline of the formation of the pituitary (left) and the various parts of the organ in the adult (right). Citation: Chapter 18 The Pituitary Gland, Barrett KE, Barman SM, Brooks HL, Yuan JJ. Ganong's Review of Medical Physiology, 26e; 2019. Available at: https:// accessmedicine.mhmedical.com/content.aspx?bookid=2525&sectionid=204292155 Accessed: August 29, 202 Copyright © 2023 McGraw-Hill Education. All rights reserved 3 Regulation of Hormone Secretion Anterior Pituitary Secretes 6 hormones Prolactin, TSH, GH, FSH, LH, ACTH Secretion is controlled by hypophysiotropic hormones : Anterior pituitary hormones. In women, FSH and LH act in sequence on the ovary to produce growth of the ovarian follicle, ovulation, and formation and maintenance of the corpus luteum. Prolactin stimulates lactation. In men, FSH and LH control the functions of the testes. ACTH, adrenocorticotropic hormone; β-LPH, β-lipotropin; FSH, follicle-stimulating hormone; LH, luteinizing hormone; TSH, thyroid-stimulating hormone. Citation: Chapter 17 Hypothalamic Regulation of Hormonal Functions, Barrett KE, Barman SM, Brooks HL, Yuan JJ. Ganong's Review of Medical Physiology, 26e; 2019. Available at: https://accessmedicine.mhmedical.com/content.aspx?bookid=2525&sectionid=204292033 Accessed: August 29, 202 Copyright © 2023 McGraw-Hill Education. All rights reserved 3 Regulation of Hormone Secretion Posterior Pituitary Stores and releases 2 hormones ADH (Vasopressin)- water balance Oxytocin- milk ejection and uterine contractions : Oxytocin Released by posterior pituitary 2 primary functions Milk ejection: triggers milk ejections from mammary glands during chest feeding Uterine contractions: helps during childbirth to support labour and delivery Role in social bonding between individuals Oxytocin - Physiology Most well-known physiologic roles ▪ Important stimulant of uterine contraction during childbirt ▪ Milk ejection from breast tissue in someone who is lactatin Both roles involve contraction of smooth muscl ▪ Receptor activation ! Gq-mediated increases in cytosolic calcium and activation of smooth muscle myosin (see next slide ▪ Calcium excites smooth muscle using different molecular mechanisms than in skeletal or cardiac muscle g h ) : e  Regulation of contraction in smooth muscle To be discussed in more depth during our vascular physiology classes  Oxytocin Physiology Kind of unique endocrine regulatio ▪ Stimulators – sensory stimulation of breast tissue (milk ejection) or pressure/thinning of the cervix ▪ Most of our other pituitary hormones respond to central signals or negative feedback n  Oxytocin Physiology Oxytocin does not exert its effect on uterine tissue until it is time for parturition (too early ! premature labour ▪ The uterus increases gap junctions and oxytocin receptors at the end of pregnancy Steadily increasing levels of estrogen ! more oxytocin receptors prostaglandin levels within the uterus also rise later in pregnancy (regulation poorly-understood) – prostaglandins also aid uterine contraction ▪ like the uterus is slowly being “primed” until secretion of oxytocin is enough to bring about the positive feedback cycle of uterine contraction and cervical thinning/dilation ) Oxytocin Physiology The regulation of oxytocin secretion is complex and knowledge is still developing… however ▪ Most of the time, significant secretion of oxytocin during pregnancy is inhibited by input from other brain regions Neurotransmitters of interest include GABA, NO, endogenous opioids ▪ This inhibition is lifted near the end of pregnancy, when estrogen levels rise and progesterone levels begin to decline ▪ Other factors that inhibit oxytocin secretion “stressors” – fear, pain, loud noise fever : : ADH- Anti-diuretic Hormone AKA Vasopressin Released by posterior pituitary Primary function Water regulation- acts on kidneys to increase water reabsorption results in decreased urine production—> prevents dehydration water balance maintenance—> blood osmolarity maintained Summary of ADH Physiology Release is stimulated by ▪ increased ECF osmolarity – most powerful stimulator, detected by osmoreceptors near the hypothalamus in the lamina terminali ▪ decreased blood pressure/volume – weaker stimulus, detected at arterial baroreceptors and venous baroreceptors (venous found in great vessels, atrial walls ADH has two major effects ▪ V1 receptor activation in vascular smooth muscle ! vasoconstriction and increased B ▪ V2 receptor activation in the kidney ! increased water reabsorption ! increased extracellular fluid volume (and decreased osmolarity) and more concentrated (and lower volume) urine s : : P ) Pituitary Tumours Why are pituitary adenomas so common? ▪ They are all monoclonal, so likely a mutation confers a growth advantag ▪ Some have activating mutations in Gs-proteins (1/3) ▪ Some seem to over-express or over-activate growth factor signaling (FGF or EGF ▪ Loss of negative feedback inhibition (increased hypothalamic releasing hormone) may play a role …but really, no one has a clear answe Rare familial syndromes (to cover with NPLEX review course) such as multiple endocrine neoplasia (MEN) involve loss of tumour suppressor genes e ) r … Pituitary Tumours - Overview Adenoma Hormones Clinical Findings, Notes Cell type Lactotroph PRL Hypogonadism, galatorrhea, mass effects Most common adenoma, most common cause of hyperprolactinemia Gonadotroph FSH, LH, beta- Usually silent – minority secrete FSH or LH subunits can result in ovarian hyperstimulation or hypogonadism, mass effects can occur Second most common adenoma Somatotroph GH Acromegaly/gigantism, mass effects 3rd most common Corticotroph ACTH Cushing’s disease, mass effects – some are silent 5th most common Mixed GH and PRL, GH Hypogonadism, galactorrhea, acromegaly, mass PRL cell effects Several subtypes – together are 4th most common Thyrotroph TSH Thyrotoxicosis Quite uncommon  Mass Effects – Pituitary Tumours As a pituitary grows in the sella the following can occur: ▪ Hypopituitarism – compression of functional anterior pituitary tissu Exception – often results in excessive function of lactotrophs – why Impingement and loss of normal pituitary function are usually early manifestations of expansio The posterior pituitary stalk can also be compressed ! diabetes insipidu ▪ Bitemporal hemianopsia – as it elevates the dura and “crushes” the lateral optic nerve Scotomas, blindness, and loss of red perception can also occur – everyone with a pituitary tumour needs a thorough eye exa Ophthalmoplegia and facial numbness can also occur as the cavernous sinus is impacted (CN III, CN IV, CN VI) ▪ Headaches are common, and they don’t correlate well to the size of the tumour m ? e s n s  FYI – contents of the cavernous sinus Lot of important stuff in there… https://commons.wikimedia.org/wiki/File:Anatomy_of_the_cavernous_sinus.jpg  Selected adenomas Lactotroph adenomas are the most common cause of hyperprolactinemia with high levels of PR ▪ See next slide for causes of hyperprolactinemia (FYI ▪ Many (more common) causes of modest increases in PRL Presentation: amenorrhea, galactorrhea, loss of libido, and infertilit ▪ Why amenorrhea & infertility? PRL inhibits GnRH secretion and directly impairs gonadal steroid productio In men, can lead to low testosterone levels, loss of fertility, and loss of libido (galactorrhea is uncommon) n y L ) Disorders of the Posterior Pituitary (FYI) No known disorders of oxytocin secretion (either too much or too little Loss of ADH action (head trauma, dysfunctional V2 receptors) ! diabetes insipidu ▪ Loss of large volumes of extremely dilute urin ▪ Urine loss can be as great as 20 L/day, and patients are extremely thirsty with serious hypotension if fluid is not replace ▪ Can be treated by intranasal inhalation of desmopressi Alcohol ingestion decreases ADH secretio Nausea and infection can cause excessive ADH release – known as the syndrome of inappropriate ADH secretion (siADH ▪ Patients do not have excessive blood volume or pressure since other physiologic mechanisms compensat ▪ Usually presents as modest hyponatremia ) ) s e e n n d Case Reflection Given this information, what is missing? The patient presents with headache, blurry vision, amenorrhea, and galactorrhea, knowing the function of the pituitary gland secretions, which of these problems can be readily explained by an over production or under production of these hormones? Which ones are left unexplained? Case Reflection Headache, Blurry vision, Amenorrhea, Galactorrhea, Knowing the function of the pituitary gland secretions, which of these problems can be readily explained by an over production or under production of these hormones? Which ones are left unexplained? Pituitary Growth Disorders Functional Disorders Definition-result from hormone-secreting tumours eg adenoma (can be micro or macro) Can lead to overproduction of hormones causing concerns like GH- Giantism (children) and Acromegaly (adults) PRL- Prolactinoma (most common ~50%) Clinical presentation and Complications Symptoms from mass effects include headache; visual loss through compression of the optic chiasm (classically a bitemporal hemianopia); and diplopia, ptosis, ophthalmoplegia, and decreased facial sensation from cranial nerve compression laterally. Pituitary stalk compression from the tumour may also result in mild hyperprolactinemia. Symptoms of hypopituitarism or hormonal excess may be present as well (see below). Non-Functional Tumours and Hypopituitarism Definition- do not secrete hormones- about 1/3 Can lead to hypopituitarism- insufficient hormone production As a result, can affect other hormones resulting in various symptoms ACTH- adrenal insufficiency- fatigue, weight loss, LBP TSH- hypothyroidism symptoms FSH and LH- sexual dysfunction and infertility Hyperpituitarism Increased hormone production Hypopituitarism Low levels of pituitary hormones These disorders may be genetic, congenital, traumatic (pituitary surgery, cranial irradiation, head injury), neoplastic (large pituitary adenoma, parasellar mass, craniopharyngioma, metastases, meningioma), infiltrative (hemochromatosis, lymphocytic hypophysitis, sarcoidosis, histiocytosis X), vascular (pituitary apoplexy, postpartum necrosis, sickle cell disease), or infectious (tuberculous, fungal, parasitic). Hypopituitarism- Clinical features Each hormone deficiency is associated with specific findings: GH: growth disorders in children; increased intraabdominal fat, reduced lean body mass, hyperlipidemia, reduced bone mineral density, decreased stamina, and social isolation in adults FSH/LH: menstrual disorders and infertility in women, hypogonadism in men ACTH: features of hypocortisolism without mineralocorticoid deficiency TSH: growth retardation in children; features of hypothyroidism in children and adults PRL: failure to lactate postpartum Sequential: GH>FSH>LH>TSH>ACTH. Diagram of pituitary axes. Hypothalamic hormones regulate anterior pituitary tropic hormones that, in turn, determine target gland secretion. Peripheral hormones feedback to regulate hypothalamic and pituitary hormones. ACTH, adrenocorticotropin hormone; CRH, corticotropin-releasing hormone; FSH, follicle-stimulating hormone; GH, growth hormone; GHRH, growth hormone–releasing hormone; GnRH, gonadotropin-releasing hormone; IGF, insulin-like growth factor; LH, luteinizing hormone; PRL, prolactin; SRIF, somatostatin, somatotropin release–inhibiting factor; TRH, thyrotropin-releasing hormone; TSH, thyroid-stimulating hormone. Citation: Chapter 171 Disorders of the Anterior Pituitary and Hypothalamus, Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Harrison's Manual of Medicine, 20e; 2020. Available at: https://login.ccnm.idm.oclc.org/ Accessed: August 29, 202 Copyright © 2023 McGraw-Hill Education. All rights reserved 3 HPG axis HPG axis POST ASSESSMENT  Quick Quiz If a patient presents with reduced bone mineral density, increased abdominal fat and decreased stamina with some possible depression, following a recent head injury – which of the following would be reasonable mechanisms to explain this presentation A. Increased prolactin secretion secondary to prolactinom B. Trauma to the somatotropes of the anterior pituitary resulting in hypopituitaris C. TSH-secreting adenoma resulting in suppression of TRH and subsequent hypopituitaris D. Side effect of starting a new antidepressant resulting in hyperprolactinemia ? m m a SUMMARY Key Points The Pituitary has 2 lobes- anterior and posterior and is controlled by the Hypothalamus The Anterior pituitary is derived from endothelial tissue and secretes 6 hormones The Posterior pituitary is a neural extension of the brain and releases 2 hormones Key Points ADH regulates water balance. Oxytocin is responsible for uterine contractions during labour and milk ejection. It also plays a role in social bonding. Causes of Hypopituitarism vary, including genetic, traumatic, congenital and neoplastic HPG axis- feedback loops and regulation  References Hypothalamic Regulation of Hormonal Functions. In: Barrett KE, Barman SM, Brooks HL, Yuan JJ. eds. Ganong's Review of Medical Physiology, 26e. McGraw Hill; 2019. Accessed August 02, 2023. “Relation to the Pituitary Gland” https://accessmedicine-mhmedical-com.ccnm.idm.oclc.org/ content.aspx?bookid=2525&sectionid=204292033 The Pituitary Gland. In: Barrett KE, Barman SM, Brooks HL, Yuan JJ. eds. Ganong's Review of Medical Physiology, 26e. McGraw Hill; 2019. Accessed August 02, 2023. “Development, structure and cell types of pituitary” https://accessmedicine-mhmedical-com.ccnm.idm.oclc.org/ content.aspx?bookid=2525&sectionid=204292155 Hypothalamic Regulation of Hormonal Functions. In: Barrett KE, Barman SM, Brooks HL, Yuan JJ. eds. Ganong's Review of Medical Physiology, 26e. McGraw Hill; 2019. Accessed August 02, 2023. “Control of Anterior Pituitary Secretion” https://accessmedicine-mhmedical- com.ccnm.idm.oclc.org/content.aspx?bookid=2525&sectionid=204292033 The Pituitary Gland. In: Barrett KE, Barman SM, Brooks HL, Yuan JJ. eds. Ganong's Review of Medical Physiology, 26e. McGraw Hill; 2019. Accessed August 02, 2023. “Pituitary Gonadotropins and Prolactin” https://accessmedicine-mhmedical-com.ccnm.idm.oclc.org/content.aspx? bookid=2525&sectionid=204292155 Disorders of the Anterior Pituitary and Hypothalamus. In: Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. eds. Harrison's Manual of Medicine, 20e. McGraw Hill; 2020. (Entire chapter, as its pretty short) Accessed August 02, 2023. https://accessmedicine-mhmedical- com.ccnm.idm.oclc.org/content.aspx?bookid=2738&sectionid=227559595