On the exam Know anterior pituitary + posterior pituitary, cells, hormones, diseases produced **Hypopituitarism, Melatonin**

Endocrine • System keeps organs in metabolic equilibrium • Signaling by extracellular:

o autocrineo Paracrineo endocrine.

Endocrine Diseases: Classified as:

o under or overproduce of hormones biochemical and clinical consequences

o or diseases associated w/ mass lesionso nonfunctional/functional

Endocrine Organs:• Pituitary• Thyroid gland• Parathyroid glands• Endocrine pancreas• Adrenal glands• Multiple endocrine neoplasia• Pineal gland.

Pituitary and HypothalamusAnatomy• Pituitary

– located in sella turcica– 2 components:

• Anterior (80% larger)• Posterior

– pituitary stalk connects pituitary + hypothalamus• Hypothalamus

– Links nervous system to endocrine system via pituitary gland.

Pituitary-Hypothalamus axis• ANTERIOR PITUIATARY

• Hypothalamus release stimulating hormone (trophic hormones) portal vascular system stimulate anterior pituitary anterior produce pituitary hormone

• Endocrine cells release hormones into the second set of capillaries for distribution to rest of the body

• POSTERIOR PITUITARY • Hypothalamus make hormones in he hypothalamus store in axon

terminal in posterior pituitary when stimulated secrete 2 peptide hormones

Anterior and Posterior Pituitary Histology• Anterior pituitary

– Hematoxylin + eosin colorful array of cells b/c different secretions– 5 cell types based on specific antibodies against the pituitary

hormones• Somatotrophs

• growth hormone (GH); 50% of cells. • Lactotrophs (mammotrophs)

• prolactin • Corticotrophs

• adrenocorticotropic hormone (ACTH)• pro-opiomelanocortin (POMC• meloanocyste stimulating hormone (MSH)

• Thyrotrophs • thyroid-stimulating hormone (TSH)

• Gonadotrophs (ovary)• follicle-stimulating hormone (FSH)• luteinizing hormone (LH)

• Posterior Pituitary**– Contain modified glial cells (pituicytes)

• b/c only stored hormones not produce– Oxytocin and Antidiuretic hormone (ADH, a vasopressin)

• Made in hypothalamus • released into systemic circulation in response to appropriate

stimuli • Labor- uterus to contract• Postpartum – to contract• Dehydration and hypovolemia – heart receptors

contract to tell body to counter dehydrationPituitary Disease• Hyperpituitarism

– pituitary adenoma– Hyperplasia– Carcinomas (less than 1%)– secretion of hormones by nonpituitary tumors– certain hypothalamic disorders

• Hypopituitarism – ischemic injury, surgery or radiation– inflammatory reactions– nonfunctional pituitary adenomas

• Local mass effects – radiographic abnormalities of the sella turcica– visual field abnormalities– elevated intracranial pressure– pituitary apoplexy

Pituitary Adenoma• most common cause of hyperpituitarism• anterior lobe• functional or nonfunctional• common cause of hyperpituitarism• peak incidence from 35 to 60 years of age• microadenomas (<1 cm in diameter) or macroadenomas (>1 cm in diameter ,

silent and hormone-negative)• classified on the basis of hormone(s) produced by the neoplastic cells,

detected by immunohistochemical stains.

Pituitary Adenomas• Genetic alteration

– Sporadic (95%)• G-protein mutations in the alpha subunit that interferes with

its intrinsic GTpase activity – Familial

• MEN1, CDKN1B, PRKAR1A, and AIP• Molecular abnormalities associated with aggressive behavior:

– over expression of cyclin D1– mutations of p53– epigenetic silencing of the retinoblastoma gene (RB1)

Pituitary Adenoma Morphology• Soft, well circumscribed• When infiltrate neighboring tissues, are called invasive adenomas• Composed of sheets/cords of uniform polygonal cells with absent reticulin

network (in contrast to normal pituitary)• Atypical adenomas if brisk mitotic activity and extensive nuclear p53

immunoreactivity, exhibit aggressive behavior• Lacks reticulum in this tumor • Large non functioning tumor • There is just one uniform population of cells

Pituitary Adenoma Clinical Effect Overproduction of hormone based on the specific types of adenomas Local mass effects radiographic abnormalities of the sella turcica visual field abnormalities elevated intracranial pressure pituitary apoplexy

Adenomas Types*• Prolactinomas

– Most common type, constitutes 30% of the cases– Increased prolactin secretion– Amenorrhea/galactorrhea/decreased libido/infertility– Other causes such as physiological/ drugs/ estrogens/ renal failure – Treatment- surgery or bromocriptine

• Somatotropinoma– Second most common type– Excessive GH (stimulates hepatic secretion of IGF-1)– Children –gigantism– Adults- acromegaly– Treatment – surgery or somatostatin analogs

• ACTH cell (corticotroph) adenomas– Usually small microadenomas at time of diagnosis– Excess production of ACTH– Hypercortisolism (Cushings disease)

• Bihormonal adenomas– PRL and G cells

• Nonfunctioning adenomas– 25-30% of all pituitary tumors– Typical presentation is mass effect

Hypopituitarism ischemic injury, surgery or radiation inflammatory reactions nonfunctional pituitary adenomas at least 75% of parenchyma is lost mostly because of destructive process tumors and other mass lesions traumatic brain injury Surgery or radiation Pituitary apoplexy (sudden hemorrhage) Ischemic necrosis

- DIC, Sickle cell anemia, Sheehan syndrome (postpartum necrosis of anterior pituitary)

Empty sella syndrome (enlarged empty ,sella turcica) Inflammatory disorders/infections Hypothalamic lesions

• Clinical manifestations– GH deficiency – dwarfism– LH and FSH deficiency- amenorrhea, infertility and others– TSH deficiency – hypothyroidism– ACTH deficiency – hypoadrenalism– Prolactin deficiency- failure of postpartum lactation

Posterior pituitary syndromes• Involves ADH

– Antidiuretic hormone binds to receptors on cells in the collecting ducts of the kidney and promotes reabsorption of water back into the circulation.

• Diabetes insipidus – losing a lot of water– ADH deficiency – loss of water – Central or nephrogenic – something wrong with hypothalamus– Loss of large volumes of dilute urine, hypernatremia, polydypsia

• Syndrome of inappropriate ADH secretion– Reabsorption of excessive amounts of free water– Water retention, hyponatremia, cerebral edema– Cause

• Excess production by CNS. • ectopic secretion by small cell carcinoma of lung• due to tumor

Lesions of hypothalamus

• Disruption of function of hypothalamic/pituitary axis– Hypopituitarism– Hyperprolactinemia

• Neurologic – Visual field defects

Hypothalamic suprasellar tumors• Clinically significant because may cause

– Hypofunction or hyperfunction of anterior pituitary– Diabetes insipidus– Includes

• Gliomas• Craniopharyngiomas –rare, slow growing tumor

• Craniopharyngioma**– slow-growing, accounts for 1-5% of intracranial tumors.– bimodal age distribution– commonly cystic and multiloculated– arises from remnants of the craniopharyngeal duct and/or Rathke

cleft

• 2 distinct histologic types:– Adamantinomatous

• Children• squamous epithelium• wet keratin and calcification• cysts contain “machine oil”

– Papillary• Adults• lack keratin• calcification• cysts

Pineal gland

• 100-180 mg pine cone shaped, located near the center of the brain, between the two hemispheres.

• pineal gland is a midline structure, and is often seen in plain skull X-rays as it is often calcified.

• The pineal body consists of a lobular parenchyma of epithelial pinealocytes and glia.

• Produces• Melatonin, a serotonin derived molecule that inhibits GnRH release.• Blood levels highest in dark • *Know that it’s for melatonin * to help you sleep

Pineal lesions• Endocrine

– Precocious puberty due to melatonin deficiency• Neurologic

– increased intracranial pressure due to mass effect• Non neoplastic cysts• Germ cell neoplasms • Pineal parenchymal tumors

Blue- hypothalamusPink-anterior hormones