Pituitary Gland diseases SMS 3023 Dr. Mohanad R. Alwan
Endocrine Glands• Controls many body functions – exerts control by releasing special chemical substances into the blood called Hormones – Hormones affect other endocrine glands or body systems• Ductless glands• Secrete hormones directly into bloodstream – Hormones are quickly distributed by bloodstream throughout the body
Hormones• Chemicals produced by endocrine glands.• Act on target organs elsewhere in body.• Control/coordinate widespread processes: • Homeostasis. • Reproduction. • Growth & Development. • Metabolism. • Response to stress. • Overlaps with the Sympathetic Nervous System
HormonesHormones are classified as: Proteins Polypeptides (amino acid derivatives) Lipids (fatty acid derivatives or steroids)
HormonesAmount of hormone reaching target tissue directly correlates with concentration of hormone in blood. Constant level hormones • Thyroid hormones Variable level hormones • Epinephrine (adrenaline) release Cyclic level hormones • Reproductive hormones
The Endocrine System Consists of several glands located in various parts of the body Specific Glands Hypothalamus Pituitary Thyroid Parathyroid Adrenal Kidneys Pancreatic Islets Ovaries Testes
Hypothalamus Produces several releasing and inhibiting factors that stimulate or inhibit anterior pituitary’s secretion of hormones. Produces hormones that are stored in and released from posterior pituitary.
Hypothalamus Also responsible for: Regulation of water balance Esophageal swallowing Body temperature regulation (shivering) Food/water intake (appetite) Sleep-wake cycle Autonomic functions
Hypothalamic Hypothalamic neural cells synthesize specific releasing and inhibiting hormones that are secreted directly into the portal vessels of the pituitary stalk. Hypothalamic-pituitary portal plexus provides the major blood source for the anterior pituitary.
Hypothalamic releasing hormonesHypothalamic releasing Effect on pituitaryhormoneCorticotropin releasing hormone Stimulates ACTH secretion(CRH)Thyrotropin releasing hormone Stimulates TSH and Prolactin(TRH) secretionGrowth hormone releasing Stimulates GH secretionhormone (GHRH)Somatostatin Inhibits GH (and other hormone) secretionGonadotropin releasing hormone Stimulates LH and FSH(GnRH) a.k.a LHRH secretionProlactin releasing hormone (PRH) Stimulates PRL secretionProlactin inhibiting hormone Inhibits PRL secretion(dopamine)
Pituitary Gland Small gland located on stalk hanging from base of brain. “The Master Gland” Primary function is to control other glands. Produces many hormones. Secretion is controlled by hypothalamus in base of brain.
Pituitary Gland• Weight 600 mg• Is located within the bony cavity (sella turcica)• Anatomically and functionally distinct anterior and posterior lobes• Anterior Pituitary-adenohypophysis• Posterior pituitary-neurohypophysis
Histology of the PG Anterior pituitary cells were originally classified as• Acidophils cells• Basophils cells• Chromophope cells
Histology of PG Now with immunocytochemical and electron microscopic techniques,classified cells by their secretary products• Somatotrophs cells• a. GH secreting cells• Account about 50% of anterior P.G• Acidophilic stained
Histology of PG• Lactotrophic• a. Prl secreting cells• b. acidophilic stained• c. 10-15% of anterior PG• Thyrotrophis• a. TSH secreting cells• b. basophilic cells• c. < 10% of anterior PG
Histology of PG• Corticotrophs a. ACTH secretary cells b. basophilic cells c. 15- 20% of anterior PG• Gonadotrophs a. LH,FSH secretary cells b. basophilic staining c. 10- 15% of anterior PG
Pituitary Development• The pituitary originate from different source.• The anterior pituitary from Rathke´s pouch (which is an embryonic invagination of the pharyngeal epithelium).• The posterior pituitary from an outgrow of the hypothalamus.
o Oxytocin, o Antidiuretic hormone• Adrenocorticotropic hormone(ACTH)• Thyroid-stimulating hormone(TSH)• Growth hormone, Prolactin• Luteinizing hormone,• Follicle stimulating hormone• melanocyte–stimulating hormones
Pituitary Gland Two areas Anterior Pituitary Posterior Pituitary Structurally, functionally different
Pituitary Gland Anterior Pituitary Hormones Thyroid-Stimulating Hormone (TSH) stimulates release of hormones from Thyroid thyroxine (T4) and triiodothyronine (T3): stimulate metabolism of all cells calcitonin: lowers the amount of calcium in the blood by inhibiting breakdown of bone released when stimulated by TSH abnormal conditions hyperthyroidism: too much TSH release hypothyroidism: too little TSH release
Pituitary Gland Anterior Pituitary Growth Hormone (GH) stimulates growth of all organs and increases blood glucose concentration decreases glucose usage increases consumption of fats as an energy source Adreno-Corticotrophic Hormone (ACTH) stimulates the release of adrenal cortex hormones
Pituitary Gland Anterior Pituitary Follicle Stimulating Hormone (FSH) females - stimulates maturation of ova; release of estrogen males - stimulates testes to grow; produce sperm Luteinizing Hormone (LH) females - stimulates ovulation; growth of corpus luteum males - stimulates testes to secrete testosterone
Pituitary Gland Anterior Pituitary Prolactin stimulates breast development during pregnancy; milk production after delivery Melanocyte Stimulating Hormone (MSH) stimulates synthesis, dispersion of melanin pigment in skin
Pituitary Gland Posterior Pituitary Stores, releases two hormones produced in hypothalamus Antidiuretic hormone (ADH) Oxytocin
Pituitary Gland Posterior Pituitary Hormones: Antidiuretic hormone (ADH) Stimulates water retention by kidneys reabsorb sodium and water Abnormal conditions Undersecretion: diabetes insipidus (“water diabetes”) Oversecretion: Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Oxytocin Stimulates contraction of uterus at end of pregnancy (Pitocin®); release of milk from breast
Pineal Gland Located within the Diencephalon Melatonin Inhibits ovarian hormones May regulate the body’s internal clock
Anterior Pituitary Isoften referred to as the “MASTER GLAND” because, it orchestrates the complex regulatory functions of multiple other endocrine glands.
Etiology Reduced pituitary function can result from inhereited disorders; more commonly, it is acquired and reflects the mass effects of tumors or the consequences of inflamation or vascular damage.
Causes of hypopituitarismTumours (tu’) Vascular ds Pituitary tumor Necrosis (Sheehan’s synd) Adenoma,craniopharyngioma Infarction Cerebral tumor Severe hypotensionHypothalamic disorders Cranial arteritis Tumor Trauma Functional disturbance-Eg -Anorexia nervosa Isolated GH and GnH secretion Infection due to impaired secretion of Meningitis esp TB, syphilis hypothalamic releasing hormones IatrogenicMiscellaneous Surgery Sarcoidosis (inflammation of L.N) Irradiation Histocytosis X (abnormal Prolonged rx with increase in the number of immune cells ) glucocorticoid or thyroid Haemochromatosis hormones-isolated ACTH or TSH suppression
Developmental and Genetic Causes of Hypopituitarism Pituitary Displasia Tissue-Specific Factor Mutations Developmental Hypotalamic Dysfunction: Kallmann Syndrome (Hypogonadotropic hypogonadism) Laurence-Moon-Bardet-Biedl Syndrome (involves many body systems) Fröhlich Syndrome (childhood metabolicdisorder) Prader-Willi Syndrome.
Acquired Hypopituitarism Trauma. Vascular Pituitary or hypothalamic neoplasms Inflammatory diseases. Infiltrative disorders such as sarcoidosis, hemochromatosis.
ANTERIOR PITUITARY HYPOFUNCTION (hypopituitarism) 3 most common causes: Non secretory adenoma of ant pituitary Sheehan’s syndrome (postpartum pituitary necrosis) Empty sella syndrome (pituitary gland become shrinks or becomes flattened)
Partial hypopituitarism is more frequent than complete loss of pit functions Sx/signs do not manifest until > 75% of ant lobe is destroyed GH secretion is an early feature of pit failure-effects > dramatic in children but less significant in adults LH/ FSH are affected before ACTH Hypothyroidism is an uncommon presenting feature of pit failure
Clinical features Hormone Features of deficiencyGH Children: growth retardation Adults: ↓muscle bulk Tendency to hypoglycaemia.Prolactin Failure of lactationGonadotrophins Children: delayed puberty Female: oligomenorrhoea, infertility,atrophy of breast & genitalia Male:Impotence,azoospermia,testicular atrophy Both sexes: LO libido,LO body hairACTH Weight loss, hypotension, hypoglycaemia, decrease skin pigmentationTSH Weight gain, cold intolerence,fatiqueVasopressin Thirst, polyuria
Posterior Pituitary hypofunction Causes ADH production cranial diabetes insipidus (DI)Causes of cranial DI Tumours-craniopharyngioma, secondary tumours (metastatic CA), pituitary tumours with suprasella extension. Granulomatous disease. Meningitis, abscess and encephalitis. Vascular disorders. Trauma. Surgery. Idiopathic.
Posterior Pituitary hypofunction Effects Polyuria-uncontrolled renal water excretion, tendency to dehydration Polydipsia-excessive thirst, dehydration stimulate thirst centre resulting in increase water intake
Key features Hypotension Decreased pulse pressure Tachycardia Increased Hbg,hct and BUN Increased UOP Poor skin turgor Irritablilty Decreased coginition Hyperthermia Lethargy leading to coma
PITUITARY HYPERFUNCTION (HYPERPITUITARISM)Hyperpituitarism - excessive production of adenohypophyseal hormones Causes Pituitary adenoma Carcinoma (rare) Hypothalamic disorder-excess stimulation of the pituitary (rare) Order of frequency with which hormone secretion occurs in pituitary tumour is prolactin (relatively common) GH ACTH gonadotrophin TSH
Consequences: a) Excessive Secretion of prolactin → ↓ secretion of GnRH → ↓gonadotrophins In men: impotency, decreased libido In women: amenorrhea, galactorrheab) Excessive Secretion of somatotrophine (growth hormone ) → acromegaly (in adults) → gigantism (in adolescents whose epiphyseal plates have not yet closed)
b)-continuing Pathomechanisms involved :-The usual GH baseline secretion pattern is lost (as are sleep – relatedGH peaks)- GH secretion is slightly elevated → ↑somatomedin → stimulation of growth (in adolescent) C. In adult s :- C onnective tissue proliferation- Bony proliferation → characteristic appearance of acromegaly- ↑Phosphate reabsorbtion in renal tubules → hyperphosphatemia- Impairement of carbohydrate tolerance- ↑ Metabolic rate- H yperglycemia - it is a result of GH inhibition of peripheral glucose uptake and increase hepatic glucose production → compensatory hyperinsulinism → → insulin resistance → diabetes mellitus
D. Excessive Secretion of corticotrophin (ACTH) → central form of Cushing syndrome (Cushing disease) Causes: micro- or macroadenomas of adenohypophysis, hypothalamic disorders Pathophysiology: C hronic hypercortisolism is the main disturbance of ↑ ACTH Symptoms and signs: • weight gain: - accumulation of adipose tissue in the trunk, facial, and cervical areas (truncal obesity, moon face, buffalo hump) - weight gain from Na and water retention • glucose intolerance → DM type 2 • polyuria: osmotic polyuria due to glycosuria
E. Protein Wasting : due to catabolic effects of cortisol on peripheral tissue (muscle wasting → muscle atrophy and weakness → thin lower extremities) → in bone: - loss of protein matrix → osteoporosis - ↑blood calcium concentration → renal stones → in skin: - loss of collagen → thin, weakened integumentary tissues → purple striae; rupture of small vesels - thin, atrophic skin is easily damaged, leading to skin breaks and ulcerationF. Hyperpigmentation: due to very high levels of ACTH - manifestationin: mucous membranes, hair, and skin • Hypertension: results from permissive effect of cortisol on the actions of the catecholamines (KA) → ↑ vascular sensitivity to KA → → vasoconstriction → hypertension
• Suppression of the immune system → ↑ susceptibility to infections • alteration of mental status - from irritability and depression up to schizophrenia• symptoms and signs of ↑ adrenal androgen s level in women: - ↑ hair growth (especially facial hair) - acne - oligoamenorrhea - changes of the vois• Hyperglycemia, glycosuria, hypokalemia, metabolic alkalosis• Excessive Secretion Of Thyreotrophin and Gonadotrophins is rare
Measurement of anterior pituitary hormones Measured in serum by immunoassay Dynamic tests/ functional tests are important tools in pituitary functions and other endocrine organs.Basic principle of dynamic tests: Hypofunction - stimulation tests Hyperfunction-suppression tests Magnetic resonance imaging (MRI)
Treatment Hormone replacement therapy, including glucocorticoids, thyroid hormone, sex steroids, growth hormone and vasopressin, is usually free of complications. Glucocorticoid replacement require careful dose adjustments during stressful events.