1. Pathology of Endocrine Systems (Pituitary).pdf

Pathology of Endocrine System  Lecture Outline B ① - - PTH ③ T4 , T3 , IT ④ ENDOCRINE DISORDERS...

Pathology of Endocrine System  Lecture Outline B ① - - PTH ③ T4 , T3 , IT ④ ENDOCRINE DISORDERS (without physiological condition) Excess hormones secretion ~ overproduction without any condition => => Originate from gland Primary hyperfunction Jeg Hyperthyroidism by thyroidgland) that produce - : caused the hormone hyperthyroidism by gland) caused pituitary Secondary hyperfunction Legenymate from - : stimulate hormone) the organ that the oufste system of hormone/normal Ectopic hormone syndromes "outside" production - pituitary/thyroid produce eg : not by from peptide source gland ; associated with cancer that minie produce function of hormone) Decreased hormones secretion # Primary hypofunction Secondary hypofunction hyperplasia Congenita adrenal disease congenital with : Enzyme deficiency eg associated of encyme > ↓ production of hormone synthesis - - enzyme > 10 - - defeet/absence of defect condition) fake (not a true defect in receptor > - gland can't Defect target organ receptors (pseudo) - - Secretion of abnormal hormones - Enzyme deficiency  MECHANISMS OF HORMONAL ALTERATIONS Abnormalities in endocrine function may be caused by elevated or depressed hormone levels that result from : faulty feedback systems /eg : signal) pituitary sland roscle , can't send dysfunctions of the gland altered metabolism of hormones production of hormones from non-endocrine tissues. Targets cells may fail to respond to hormones because of: a) cell – surface receptors associated disorders b) intra – cellular disorders, or c) circulating inhibitors 193 ! to > - go PART 1 : DISORDERS OF PITUITARY GLAND  Alteration Hypothalamic – Pituitary system A.P P.P Anterior Pituitary Posterior pituitary 1. Hypopituitarism 1. SIADH C 2. Hyperpituitarism 2. Diabetes Insipidus - Agromegaly - prolactinoma syndrome ofinappropriat a secretion a (tumor at PG that produces prolactin  DISORDERS OF POSTERIOR PITUITARY SIADH Diabetes Insipidus  SIADH 1. Syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH) 2. Increased ADH levels without normal physiologic stimuli A 3. Normal condition: ADH is secreted to prevent water loss in the kidneys. 4. Water is taken up into the circulation and results in a dilution of the plasma - REDUCED PLASMA OSMOLALITY – give signal to hypothalamus – stop ADH secretion. 5. In SIADH – the release of ADH is not inhibited by reduced plasma osmolality 6. Common cause : ECTOPIC production SIADH – CLINICAL MANIFESTATION HYPOOSMOLALITY - HYPONATREMIA - - URINE HYPEROSMOLARITY HYPERVOLEMIA -  Treatment SIADH – EVALUATION & TRX - Serum electrolyte Serum osmolality Urine volume Urine osmolality Urine electrolyte Treatment - CORRECTING HYPONATREMIA AND HYPERVOLEMIA. - Hypertonic saline - Fluid restrictions  Diabetes Insipidus banyak kencing cepat haus Low ADH – polyuria + polydipsia - Neurogenic / central form = absence ADH as in pituitary / hypothalamus disorders Nephrogenic form = low response renal & tubules to ADH as in renal diseases  Clinical manifestation Polyuria Banyak Kencity Nocturia Kencing malam Polydipsia haus Cepat Kensing air low urine osmolality / high serum osmolality inflammation of nephron Long term – hydronephrosis + large bladder  Disease A.P : Hypopituitarism Hypopituitarism Rare disorder in which your pituitary glands fails to produce one (isolated) or more (multiple) of its hormone or absence production for all hormones (panhypopituitarism). Etiology can be Primary / secondary Hypopituitarism can be inherited, but is more commonly seen from a tumor on the pituitary gland. Other causes include: – Head injuries – Tuberculosis – Meningitis – Stroke – Sheehan's Syndrome (postpartum pituitary necrosis) – impaired artery supply to A.P due to severe blood loss or extremely low blood pressure during / after childbirth.  CLINICAL MANIFESTATION Some symptoms do vary depending on the hormone(s) that are affected. They include: Fatigue & Loss of Appetite Weight Loss - [FLAWS] Anemia & Short stature in children - Pan hypopituitarism = absent all hormones MOST clinical features associate with function of respective gland Laboratory Investigation Blood Tests - To help detect low hormone levels Dynamic Testing - To detect hormone levels after taking hormone medication Brain Imaging - To detect a pituitary tumor or other abnormality Vision Test - To determine if the pituitary tumor has impacted your vision Treatment - hormonal replacement therapy  Disease A.P : Hypopituitarism Consequences - they depend on the affected hormones if all hormones are deficient it’s known as panhypopituitarism: - the patients suffer from: cortisol deficiency - because of lack of ACTH ; impaired metabolism thyroid hormones deficiency - because of lack of TSH : impaired metabolism deficiency of FSH and LH - gonadal failure and loss of secondary sex characteristics deficiency growth hormone (they affect children growth) absence of prolactin - postpartum women are unable to lactate  HYPOPITUITARISM 1- DWARFISM Reduced Growth hormone during childhood Characterized by: Proportionate dwarfism (short stature) Features of body are proportionate to each other, but rate of development is decreased. No thyroid or adrenocortical deficiency. No mental retardation Treatment Synthetic Growth hormone  Disease A.P : Hyperpituitarism Commonly caused by Pituitary Adenoma High Growth Hormone production Adult - Acromegaly Bony proliferation Children – gigantism Excess skeletal growth Diabetes Mellitus – stimulate glucose production [ABCDE]  Disease A.P : Hyperpituitarism Gonadotropin Consequences: ⑦ GnRH Releasing Hormone excessive secretion of prolactin and GnRH no erection in men: impotency, decreased libido tak period banyak susu In women: amenorrhea, galactorrhea excessive secretion of somatotrophine (growth hormone) causes acromegaly (in adults) and gigantism (up to adolescents stage)  HYPERPITUITARISM 1- Gigantism (Vertical Growth) Cause: Pituitary Adenoma Secretes excessive GH / IGF-1 Non cancerous. Average brain size Skull grows but brain size stays the same, thus the brain function is unaffected. All body tissues grow rapidly i.e. general overgrowth of skeleton-person becomes a Giant. High BMR (direct effect of GH on metabolic activity + effect of TSH).  HYPERPITUITARISM 1- Acromegaly (Lateral Growth) Acro = extremity as hands and feet. Megaly = large. ↑↑ GH → Bone lengthening stopped. Bone width increases. Slow progression Bone thickening Hands and feet are enlarged(thick, broad fingers) big hands may reach a level below knees. Bigger tongue and lips that affects breathing Cartilages in nose and ears enlarge making nose and ears broader. Impaired muscle movements  PROLACTINOMA High prolactin > 200ng/ml (Prolactinemia) tak period banyaksusu berbuly Cause ammenorhea, galactorrhea, hirsutism (low estrogen). Evaluation - Prolactin serum - MRI to locate tumor  Pituitary Function Test To assess functional state of Pituitary Gland it is important to: üUse simple screening tests (static test) to eliminate other courses, before using more complicated Dynamic Tests. üIf Pituitary disorder is suspected, then damage to Pituitary Functions should be assessed. Fig. 1: Hypothalamic-Anterior Pituitary Axis: Showing Releasing Hormones and corresponding Anterior Pituitary hormones  How is Pituitary Function Assessed? Current Biochemical recommendations for assessing Anterior Pituitary function: ü Measure plasma levels of Basal Anterior Pituitary Hormones; ü Measure plasma level of Hormone produced by the corresponding Primary Target Organ; ü Stimulation tests: 1. Pituitary Anterior : IV administration of Insulin, GnRH and TRH (Triple Function Test) 2. Posterior Pituitary : Water Deprivation Tests  Triple Function Tests Ø If Hypopituitarism is suspected in a patient, combined Pituitary Function Test (PFT) / Triple Function Test should be requested; Ø Combined PFT is used to assess the Anterior Pituitary reserve for production of Anterior Pituitary Hormones as follows: Insulin stimulation test – to measure ACTH / cortisol, GH, GnRH stimulation test – to measure FSH,LH, TRH stimulation test - to measure TSH, T4, PROLACTIN  What is fluid deprivation test? Test to check regulation of fluid balance and power of the kidney tubules to concentrate the urine; Regulation of fluid balance involves Arginine Vasopressin (AVP) produced in Posterior Pituitary; Test must be done only under medical supervision as it can potentially cause dehydration, fluid and salt imbalance;  Procedure Fluid Deprivation Test Test carried out after overnight fasting with no fluid intake; Collect blood and urine at 09.00am; Allow patient to consume only dry foodstuff without any fluid up until 4.00 pm; Obtain Body weight of patient, Measure Urine output every hour; Collect blood samples every hour;  How is the fluid deprivation test results interpreted? How is the fluid deprivation test results interpreted? ü Healthy individuals: Hourly urine output will drop and will become more concentrated due to lack of fluid intake; Body weight and blood concentration will remain the same; ü Patient with Diabetes Insipidus due to lack of AVP: Production of large volume of urine continues despite no intake of water; Urine remains diluted, body weight falls and blood become more concentrated as they become dehydrated Additional procedure: üAt 4.00pm DDAVP (1-Deamino, 8-D-Argenine Vasopressin; will be injected and patient allowed to take fluid; üUrine and blood collections will continue up until 20.00hr; üAim is to assess body’s response to lack of fluids and the response after injection of DDAVP; Further Interpretation of results Results may be interpreted as: üUrine Osmolality less than 300mosmol/kg after fluid deprivation, and Greater than 800mosmol/kg after Desmopressin suggests Cranial Diabetes Insipidus; üUrine Osmolality less than 300mosmol/kg after fluid deprivation, and Less than 300mosmol/kg after Desmopressin suggests Nephrogenic Diabetes Insipidus;