Endocrine System Pituitary Pineal

Antidiuretic hormone (ADH, arginine vasopressin)

Is released in response to increased blood tonicity, sensed by osmoreceptors in the hypothalamus, which stimulates ADH synthesis Increases the permeability of the renal collecting ducts to water, so that more water is reabsorbed from the filtrate in these tubules and osmotic balance of the body fluids is restored

Thyrotrophs

Least abundant cell type in the pars distalis Produce Thyroid stimulating hormone (TSH or thyrotropin)

Hypothalamus

Located below the thalamus, is a thin plate of neural tissue with a collection of nuclei consisting of neurosecretory cells Has prominent role in the regulation and control of many body's key processes Also controls the pituitary gland through the production of the releasing (stimulating) and inhibitory hormones by neurosecretory cells that stimulate or inhibit the synthesis and release of pituitary hormones, which then control the release of hormones from other endocrine glands

Diffuse neuroendocrine system

Located in the Gastrointestinal tract and Respiratory system Many of these cells have common metabolic features like Amine precursor uptake and decarboxylation (APUD system)

Metastatic spread to pituitary

Not uncommon Neurohypophysis more commonly affected Clinically they are distinguished from primary pituitary adenomas by the prominence of diabetes insipidus, and mass effects such as headaches, visual field defects, ptosis, and ophthalmoplegia The most common sites of origin are lung, breast, and gastrointestinal tract

Craniopharyngioma

Originates from the remnants of Rathke's pouch Most common sellar tumor in children and accounts for 10% of all childhood CNS tumors By LM, the tumor is characterized by islands of epithelial cells and cysts within a loose fibrous stroma By immunohistochemistry, the presence of cytokeratin reactivity confirms the epithelial nature of these tumors Ultrastructural examination reveals tonofilaments, intercellular junctions, and the absence of secretory granules Benign but locally invasive tumor The natural history of these lesions is extensive infiltration with significant tissue damage Mass effects (headaches, visual field defects) and Hypopituitarism is identified in most patients Other features include Calcification Detected by CT scan to determine the extent of the lesion MRI is the preferred

Primary endocrine glands

Pituitary gland (Hypophysis) Pineal gland (Epiphysis cerebri) Thyroid gland Parathyroid glands Adrenal glands

Gonadotrophs

Produce Follicle stimulating hormone (FSH) Luteinizing hormone (LH) called Interstitial cell-stimulating hormone (ICSH) in males Most abundant cell type in the Pars tuberalis

Melatonin

Production by pineal gland Stimulated by darkness Inhibited by light Secretion Peaks in the middle of the night (around 2:00 AM) Gradually falls during the second half of the night Diurnal fluctuation in blood induces rhythmic changes in the activity of the Hypothalamus, pituitary gland, and other endocrine tissue that characterize the circadian (24 hours, day/night) rhythm ofphysiological functions and behaviors Decreased production in the elderly causes them to sleep less and wake up more often Beneficial effects in the treatment of sleep disorders (jet lag, shift work) At low doses (0. 5 mg/day) No short term (up to 3 months) side effects At high doses (3 mg / day) Side effects Headaches, nausea Next -day grogginess Irritability Reduced blood flow Extremely high doses (50 mg / day) Vivid dreams Synthesis increased by Many psychoactive drugs (cannabis, lysergic acid diethylamide) Antioxidant activity Stimulates the activity of Glutathione peroxidase (putatively the most important antioxidant in brain)

Pituitary carcinoma

Rare malignant tumor Generally present initially as pituitary adenoma Can be associated with any form of hormone excess Only identified as malignant with the development of metastases

Functioning corticotroph adenomas

Represent 10 to 15 % of all pituitary adenomas Most common cause of Cushing's disease, defined as pituitary-dependent hypercortisolism

Functioning somatotroph adenomas

Represent 10 to 15% of pituitary adenomas In children (before epiphyseal plate closure) GH excess results in Gigantism In adults GH excess manifests as Acromegaly

Neurohypophysis

Resembles the nervous tissue Has two parts Pars nervosa that contains unmyelinated axons that run down from neurosecretory neurons whose cell bodies are in two hypothalamic nuclei and Pituicytes or specialized glial cells with round or oval nuclei that express TTF-1 protein (thyroid transcription factor 1) Infundibular stalk a funnel-shaped structure divided into Pars tuberalis and Pars infundibularis

Pars tuberalis

Small funnel-shaped region that wraps around the infundibular stalk of the neurohypophysis Gonadotrophs Most abundant cell type

Suckling stimuli

Stimulates Oxytocin synthesis by hypothalamus and Myoepithelial cell contraction, ejecting milk from alveoli into the lactiferous ducts (milk ejection reflex)

Corticotrophs (adrenocorticolipotrophs)

Synthesize Pro-opiomelanocortin (POMC) POMC is cleaved into Adrenocortical trophic hormone (ACTH) (MSH) and b-lipotropin (b-LPH) Most abundant cell type in the Pars intermedia

Corpora arenacea

(brain sands) are concretions of Ca and Mg salts formed by mineralization of extracellular protein deposits that increase in number and size with age Can be used as landmarks for the midline location of the pineal gland in X-ray of the brain

Parts infundibularis

(infundibular stem) An extension of the nervous tissue of the tuber cinereum / median eminence of the hypothalamus Contains unmyelinated axons of the magnocellular neurons of the supraoptic and paraventricular hypothalamic nuclei

Pituitary Gland

A bean shape gland surrounded by a very thin capsule of dense irregular CT and a dense plexus of thin-walled veins contained in the loose CT between the capsule and periosteum lining the hypophyseal fossa of the sella turcica Weight ~ 0.5 g in adults Attached to hypothalamus by the Infundibular stalk Consists of two parts with different embryological origin the Adenohypophysis (anterior lobe) and Neurohypophysis (posterior lobe)

Infundibular stalk

A funnel-shaped structure divided into Pars tuberalis and Pars infundibularis Ventral downgrowth from the floor of 3rd ventricle Grows toward the stomodeum Remains attached to the developing hypothalamus Gives rise to the Neurohypophysis

Pineal Gland

A small cone shaped endocrine gland ~ 6-8 mm long Develops from neuroectoderm in the posterior wall of the Lacks blood-brain barrier Attached to diencephalon by the pineal stalk Covered by CT of the piamater from which septa containing venules and capillaries extend into the gland that is divided into lobules Contains Pinealocytes Astrocytes Unmyelinated tracts of sympathetic fibers are associated indirectly with the photoreceptors run along the septa to the pinealocytes to stimulate melatonin release in periods of darkness

Pars intermedia

A thin basophilic zone between the pars distalis and the pars nervosa of the neurohypophysis, rudimentary in adults Most abundant cell type is Corticotrophs that synthesize Pro-opiomelanocortin (POMC) whcih is cleaved to ACTH MSH and gamma-lipotropin and beta-endorphin Usually has Colloid-filled cysts (<5 mm) Formed as result of the proliferation of the cells of the anterior wall of the Rathke's pouch that reduces its lumen to a narrow cleft

Chromophobes

Account for 40-50 % of cells Is a heterogenous group of unstained or weakly stained cells with few or no cytoplasmic secretory granules Thought to represent Acidophil and basophilic cells in a dormant or recently degranulated stage Stem cells of the secretory cells

Non-Functioning pituitary adenomas

Account for approximately one third of all pituitary adenomas Tend to present with mass effects such as Headache, visual field deficits, cranial nerve defects, or rarely, cavernous sinus syndrome Patients may have varying degrees of hypopituitarism depending on the amount of adenohypophysial tissue destruction Diagnosis is based on Morphologic features of the tumor

Functioning thyrotroph adenomas

Account for less than 1 % of all pituitary adenomas Most are invasive macroadenomas that cause mass effects with visual field disturbances at presentation Thyroid function tests should be performed in all patients with elevated serum levels of TSH to exclude primary thyroid failure

Basophils

Account for ~ 10-20 % of cells in the adenohypophysis Subtypes Thyrotrophs Gonadotrophs Corticotrophs (or adrenocorticolipotrophs)

Pars distalis

Accounts for ~ 75 % of the adenohypophysis Structure consists of Cuboidal endocrine cells arranged in irregular cords between a network of fenestrated capillaries and scant supporting reticular connective tissue Cells are grouped into Chromophobes and Chromophils that are further divided into Acidophils and Basophils Are secretory cells in which hormone, stored in cytoplasmic granules, is responsible for their staining characteristics

Lactotrophs (or mammotrophs)

Acidophil of the adenohypophysis Secrete prolactin (PRL) Increase significantly in number in late pregnancy and early months of lactation

Conditions affecting neurohypophysis

Affected by Head trauma, including brain surgery Compression from tumor in adjacent tissues Mutations in the gene for ADH (vasopressin)-neurophysin These conditions can lower the levels of vasopressin causing Diabetes insipidus

Melatonin and sexual activity

Appears to inhibit the release of Hypothalamic gonadotropin releasing hormone Decreased secretion of LH and FSH Weaker sexual activity

Hormones

Are complex chemical substances synthesized and secreted by endocrine cells Travel via bloodstream to specific target organs, which has cells possessing the appropriate receptor Induce physiological changes in specific target cells and then are metabolized Have specific functions such as regulation of body growth and development, reproduction, physiological cycles, and metabolic processes

Peptides and protein hormones

Are made of variable length amino acids chain Most hormones are peptides Secreted by many tissues ADH (vasopressin), GH, PTH, TSH, insulin

Acidophils

Are rounded cells and typically smaller than basophil cells Account for ~ 40% of the cells in the adenohypophysis Subtypes Name according to their hormone's target cells Identified by their granular morphology in TEM or by immunohistochemistry Somatotrophs Most frequent type of acidophils Produce Growth hormone (GH, or somatotropin, STH) Can be stained with the dye orange G Lactotrophs or mammotrophs Secrete prolactin (PRL) Increase significantly in number in late pregnancy and early months of lactation

Endocrine cells

Are secretory cells, epithelial in origin with the exception of the adrenal cortex which is mesodermally derived Release their products usually by exocytosis and basally which allows secretion to go through the basal lamina, move into the underlying connective tissue, enter the capillary network and move to target organs Their specific appearance depends on the nature of the secretory product and on the cellular machinery need to manufacture and store that product Classified according with the chemical structure of their secretory products into two histologically well characterized groups Peptides and protein secreting cells and Steroid secreting cells A diverse group of cells synthesize hormones from Amino acids, Vit A, and Retinoic acid

Functioning lactotroph adenomas

Are the most common type An elevated serum level greater than 250ng/mL (5000mU/l) is virtually diagnostic of a prolactin secreting adenoma More common in females, who tend to present at a younger age with hormonal disturbances In men tend to present later, with larger tumors that more often result in mass effects and hypopituitarism secondary to adenohypophysial destruction

Herring bodies

Are visible by LM along the trajectory and at the terminals of the axons of the Hypothalamic-hypophyseal tract as light eosinophilic ovoid granular swellings Release Oxytocin and ADH for uptake by the fenestrated capillaries of the pars nervosa upon neural stimulation Oxytocin is bound to carrier protein neurophysin 1 and ADH bound to carrier protein neurophysin 2 are transported axonally in neurosecretory granules

Pituitary adenomas

Benign tumors Arise from adenohypophysial cells Represent up to 25% of all intracranial tumors, present in approximately 17% of the general population Prevalence increases with advancing age; both sexes are affected equally Can be classed into Non- Functioning pituitary adenomas and Functioning pituitary adenomas

Diabetes insipidus

Characterized by inability to concentrate urine, leading to frequent urination (polyuria) Increased thirst (polydipsia) Also seen in 25% of patients with Craniopharyngioma

Parts tuberalis

Considered to be part of adenohypophysis, surrounding anteriorly and superficially the pars infundibularis Contains Endocrine secretory cells

Endocrine glands

Consist of clumps or cords of secretory cells surrounded by a rich vascular network An exception is the thyroid, where the epithelium does form follicles into whose lumens thyroglobulin is secreted for storage

Hypothalmic hypophyseal portal system

Consists of two capillary networks connected by the hypophyseal portal veins The primary plexus is formed in the median eminence and infundibular stalk by fenestrated capillaries from Superior hypophyseal arteries Receives the releasing and inhibiting hypothalamic hormones The capillaries of the primary plexus rejoin in the infundibular stalk to form 20 or more Portal veins that branch again as Secondary capillary plexus in the adenohypophysis Transport the hormones to the secondary capillary plexus where they diffuse to either stimulate or inhibit hormone release by the cells of the adenohypophysis

Supraoptic nucleus

Contains Magnocellular neurons that produce Antidiuretic hormone, ADH (arginine vasopressin)

Paraventricular nucleus

Contains Magnocellular neurons that produce Oxytocin

Pars infundibularis

Contains the unmyelinated axons of the magnocellular neurons of the supraoptic and paraventricular nuclei that form the Hypothalamic-hypophyseal tract

Rathke's cleft cyst

Cystic lesion of the pituitary Lined by ciliated cuboidal or columnar epithelium with occasional goblet cells Most common in adults Are non-functional but as they enlarge may cause hypopituitarism or diabetes insipidus by compression of surrounding structures

Steroid hormones

Derived from cholesterol by a biochemical reaction series Once synthesized, they pass directly into bloodstream; they are not stored by cells, and the rate of synthesis controls them Gonadal hormones, suprarenal cortex hormones

Conditions of pineal gland

Destructive lesions are associated with precocious puberty Tumor (usually germinomas) are associated with delayed puberty

Astrocytes in pineal gland

Fewer than pinealocytes, represent ~ 5 % of the cells Located mainly within the septa, near the capillaries Have Darker and more elongated nuclei

Secondary endocrine glands

Form discrete clusters within other organs Includes Pancreas Gonads Thymus Heart Kidneys Placenta

Rathke's pouch

Formed by an invagination of the thickened ectodermal cells of the roof of the stomodeum Grows toward the infundibulum Loses connection with stomodeum Cells of the Anterior wall proliferate extensively and reduces the lumen of Rathke's pouch to a narrow cleft represented by small cysts in the pars intermedia Gives rise to the Pars distalis of the adenohypophysis An outgrowth of the anterior wall extends up and wraps around the infundibular stem to form the Pars tuberalis Posterior wall does not proliferate Gives rise to thin Pars intermedia

Endocrine System

Group of ductless glands and group of cells that regulate body processes by secreting chemical substances called hormones which act as signaling molecules Comprises Primary or known endocrine glands Secondary endocrine glands and Diffuse neuroendocrine system Act together with the nervous system to coordinate functions of all body systems The link between these two systems is the Hypothalamus Controls activities that require long duration by secreting hormones which are slower acting than nerve impulses The response to an endocrine signal occurs within minutes to hours

Chromophils

Grouped into Acidophils and Basophils Subtypes are named according to their hormone's target cells

Amino acids derivatives hormones

Hormones derived from Phenylalanine, tyrosine: adrenal medulla hormones, thyroid hormones Tryptophan: pineal gland hormones, serotonin Stored as cytoplasmic granules until needed

Pituitary Hyperplasia

Increase in the number of cells of an organ or tissue in response to a stimulus Can be physiological or pathological and when prolonged may progress to adenoma formation and usually reversible when the underlying condition is appropriately treated Lactotroph hyperplasia Physiologic during pregnancy or other conditions of estrogen excess Corticotroph hyperplasia is a cause of Cushing's disease It is also physiological in patients with untreated Addison's disease Gonadotroph hyperplasia seen in patients with prolonged primary hypogonadism Somatotroph hyperplasia seen in patients with ectopic production of GH-releasing hormone (GRH) by pheochromocytomas, endocrine tumors of lung, pancreas or other elements of the diffused endocrine system Is distinguished from adenoma with the reticulin stain Typically shows expanded acini with an intact reticulin framework whereas adenomas have breakdown of the reticulin fiber network

Adenohypophysis

Is highly cellular and has a typical glandular appearance Has three parts Pars distalis or anterior lobe Pars tuberalis Pars intermedia All known hormones of the adenohypophysis are proteins or glycoproteins FSH, LH, and TSH are glycoproteins, thus stained with PAS Except for the gonadotrophs and the corticotrophs, cells of the adenophypohysis synthesize one kind of hormone The secretory activity of the cells of the adenohypophysis is controlled by Hypothalamic hormones taht are either Releasing hormones or Inhibiting hormones Delivered to the adenohypophysis through the hypothalamic - hypophyseal portal system

Functioning gonadotroph adenomas

Mainly diagnosed in middle-aged men with no prior history of gonadal dysfunction In women, the clinical diagnosis is more often missed because elevation of gonadotropins is considered to be physiological in postmenopausal women and the tumors are considered to be nonfunctional

Pinealocytes

Most abundant cell type Have Slightly basophilic cytoplasm Irregular euchromatic nuclei Long cytoplasmic processes extending to the vascularized septa, where they end in dilations near capillaries TEM reveals many mitochondria and secretory vesicles Produce melatonin, a low-molecular weight tryptophan derivative

Negative Feedback

Most common method of control of secretion

Somatotrophs

Most frequent type of acidophils Produce Growth hormone (GH, or somatotropin, STH) Can be stained with the dye orange G

Sheehan's syndrome

Vascular disorder of the pituitary Is postpartum necrosis of the pituitary gland Usually related to hypotension caused by postpartum hemorrhage Central necrosis of the gland with a rim of viable cells at the periphery Clinical manifestations appear only with significant tissue destruction The neurohypophysis, with its independent blood supply, is usually spared

Peptides and protein secreting cells

Well-developed rER in the basal cytoplasm Prominent supra-nuclear Golgi complex Membrane-bound secretory granules in the apical cytoplasm

Steroid secreting cells

Well-developed sER in the basal cytoplasm Prominent mitochondria and abundant lipid droplets Cytoplasm Granular, pink, vacuolated appearance