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Diabetes Insipidus
- 1. Emergency Lecture Series Disordersof the Pituitary By Ame M. (BSc, MSc in EMCC)
- 2. Hypothalamus and Pituitary Thehypothalamus-pituitary unit is the most dominant portion of the entire endocrine system. The output of the hypothalamus – pituitary unit: regulates the function of the thyroid, adrenal and reproductive glands controls somatic growth, lactation, milk secretion and water metabolism.
- 3. Hypothalamus and Pituitary….. Pituitary function depends on the hypothalamus The pituitary gland lies in a pocket of bone at the base of the brain, just below the hypothalamus to which it is connected by a stalk containing nerve fibers and blood vessels. lies at the base of the skull in the sellaturcica, within the sphenoid bone. weighs 500-900 mg composed of two lobes Anterior pituitary Posterior Pituitary Anatomically and functionally anterior and posterior lobes are distinct structures.
- 4. Pituitary Development The pituitaryoriginate 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.
- 5. Pituitary Gland 1. Theanterior lobe consists 2/3 of the gland originate from Rathke´s pouch (which is an embryonic invagination of the pharyngeal epithelium). Secretes A) Adrenocortico Tropic Hormone (ACTH) B) Growth hormone (GH) C) Prolactin (Prl) D) Thyroid stimulating hormone (TSH) E) Follicle stimulating hormone (FSH) F) Luteinizing Hormone(LH)
- 6. Posterior Pituitary/Lobe 2. PosteriorPituitary/Lobe consists of neural tissue & is an extension of hypothalamus. originate from an outgrow of the hypothalamus is composed of nerve fibers that have their cell bodies in the supraoptic and paraventricular nuclei of the hypothalamus. The neurosecretory cells in these nuclei synthesize Oxytocin and Vasopressin which pass down the nerve fibers to be stored in and released from the posterior pituitary.
- 7. Posterior Pituitary/Lobe secretes – Antidiuretichormone (ADH) also called arginine vasopressin (AVP) & regulates water metabolism Oxytocin controls lactation or milk ejection from breasts uterine contraction
- 8. ADH The supraopticnucleus (SON) is responsible predominantly for the synthesis of vasopressin which is the ADH. The close structural similarity of vasopressin and oxytocin explains the overlap of their biological actions. ADH is an octapeptide like oxytocin. The Arginine Vasopressin (AVP) is ADH in man and other mammals apart from the pig and the hippopotamus where Lysine Vasopressin is the ADH.
- 9. FUNCTION/ACTION OF ADH Primaryeffect of ADH is on the cells of the distal tubules and collecting ducts of the kidney promoting reabsorption of water. This action is mediated via V2-receptors and formation of a specific protein known as aquaporin. Beside water, AVP enhances reabsorption of urea increasing tonicity of the renal medulla allowing more water to be re-absorbed.
- 10. FUNCTION…… Acting onV1-receptors in peripheral vessels AVP causes vaso-constriction and increase in BP. Normally this is balanced by its inhibitory effect on sympathetic cardiac stimuli causing bradycardia. During hypovolemia high plasma levels of AVP help maintain tissue perfusion. A lesser 2ndry effect that is mediated via V2 non-renal receptors is stimulation of synthesis and release of factor VIII & Von Willebrand Factor.
- 11. REGULATION OF ADHSECRETION ADH release is stimulated by: A plasma osmolality >280 mosm/L A fall in plasma volume Emotional factors & stress Sleep Other factors Other ADH Stimulants Cholinergic stimulation -adrenergic stimulation Angiotensin II Prostaglandin E Opiates Nicotine Histamine Ether Phenobarbitone
- 12. ADH SECRETION ISINHIBITED BY: Alcohol Oropharyngeal water reflex β-adrenergic stimulants Atrial natriuretic factor (ANF) Phenytoin
- 13. Disorders of thePosterior Pituitary
- 14. Outline Diabetes Insipidus Definitions Causes Types Ass’t andDx Mgt SIADH Definitions Causes Dx Mgt
- 15. Diabetes Insipidus (DI) Definitions DIis a condition ch’rized by excessive thirst and excretion of large amounts of severely dilute urine, with reduction of fluid intake. DI is a disorder resulting from deficiency of ADH or its action ch’zed by the passage of copious amounts of dilute urine It must be differentiated from other polyuric states Primary polydipsia and Osmotic diuresis.
- 16. Diabetes Insipidus (DI) Diabetesinsipidus (DI) results from a group of disorders in which there is an absolute or relative deficiency of ADH (called central DI) or there is an insensitivity to its effects on the renal tubules (called nephrogenic DI) may complicate the course of critically and acutely ill patients and can result in acute fluid & electrolyte disturbances.
- 17. DI … Classification Different typesof DI, each with a different cause. Neurogenic/Central DI: most common Nephrogenic DI: second most common Dipsogenic DI Gestational DI
- 18. Neurogenic DI more commonlyknown as central DI, caused by a deficiency of Arginine vasopressin(AVP) AVP also known as ADH. ADH-deficient is due to a lack of vasopressin production in the brain is due to failure of the pituitary gland to secrete adequate ADH. secondary to Panhypopituitarism
- 19. Etiology of CentralDI Idiopathic (30% of cases) Suprasellar tumours (30% of cases) Hypothalamic or pituitary tumors — craniopharyngioma, germinoma, histiocytosis, glioma, lymphocytic hypophysitis. Autoimmune Associated with thyroiditis Antibodies target ADH-producing cells. Familial (hereditary): 2 types AD and X-linked inheritance Genetic (autosomal dominant inheritance) Genetic — mutations in vasopressin gene and WFS1 gene (Wolfram syndrome) Midline brain defects — septo-optic dysplasia, holoprosencephaly
- 20. Etiology of CentralDI….. Neoplasms Infections Tuberculosis Cryptococcosis Syphilis CNS infections Granulomatous diseases Infectious Granulomatous Ds (e.g., sarcoidosis, TB) Non-infectious granuloma e.g. Sarcoid, hand-schuller Christian disease (histiocytosis) Langerhans cell histiocytosis – in which 25% of pts develop DI.
- 21. Etiology of CentralDI…… Brain injury, infection, or surgical resection Infections (Encephalitis, meningitis, TB, etc) Trauma and hypoxic ischemic brain injury Trauma or skull surgery basilar skull fractures, neurosurgical complications Leukemia Vascular Ds (e.g., aneurysms, lesions) Cerebrovascular hemorrhage Aneurysm (circle of Willis) Cerebral thrombosis Wolfram syndrome (also known as DIDMOAD syndrome) ch’zed by DI, DM, Nerve Deafness and Optic Atrophy.
- 22. Nephrogenic DI ischaracterized by renal tubule insensitivity to ADH and develops because of structural or functional changes in the kidney. This results in impaired urine-concentrating ability & free water conservation. is less dramatic than neurogenic DI in its onset and appearance. ADH-resistance (kidney does not respond to ADH) is due to inability/insensitivity of the kidneys to respond normally to ADH is due to the renal tubules of the kidneys fail to respond to circulating ADH. can also an iatrogenic artifact of drug use The resulting renal concentration defect leads to the loss of large volumes of dilute urine. This causes cellular and extracellular DHN and hypernatremia.
- 23. Causes of NephrogenicDI Primary Familial (hereditary): X-linked recessive that is severe in boys and mild in girls. Secondary to: Renal disease chronic pyelonephritis chronic renal failure, obstructive uropathy, polycystic disease Electrolyte disorders Hypokalemia Hypercalcemia Sickle cell disease Protein deprivation Amyloidosis Drugs: Lithium, Colchicine, Fluoride, Rifampin, Cidofovir, Demeclocycline Methoyflurane, Cisplatin, Methicillin Amphotericin B, Gentamicin, Furosemide
- 24. CAUSES OF NEPHROGENICDI Nephrogenic DI Inherited as an X-linked recessive disorder chronic renal disease with failure to concentrate urine. Polydipsia, polyuria (>2 L/m2/day), nocturia. Patients unable to produce concentrated urine during fluid restriction. Urine SG remains <1.010 with urine osmolality <600 mOsm/kg even with plasma osmolality >300 mOsm/kg Hypernatremia and DHN with serum Na ~180 mEq/L Low serum vasopressin level
- 26. Etiology … Excessive WaterIntake (Secondary DI) Excessive IV fluid administration Psychogenic polydipsia (lesion in thirst center)
- 27. Dipsogenic DI is dueto a defect or damage to the thirst mechanism, which is located in the hypothalamus. This defect results in abnormal increase in thirst and fluid intake that suppresses ADH secretion and increases urine out put. Desmopressin is ineffective, and can lead to fluid overload as the thirst remains.
- 28. Gestational DI only occursduring pregnancy. While all pregnant women produce vasopressinase in the placenta, which breaks down ADH, this can assume extreme forms in GDI.
- 29. CLINICAL FEATURES Polyuria,polydipsia & thirst Nocturia or nocturnal enuresis Hypernatremic DHN Anorexia, constipation and FTT Hyperthermia and lack of sweating Symptoms of underlying cause Abnormalities of the CNS such as: irritability, altered consciousness, increased muscle tone, convulsions, and coma occur secondary to hypernatremia. these findings correlate with the degree and rapidity of the rise in serum Na.
- 30. COMPLICATIONS Hypernatremic DHN andits neurological sequelea Growth retardation Hydronephrosis (due to excessive urine output)
- 31. Differential Diagnosis Psychogenic polydipsia Osmoticdiuresis Diabetes mellitus Beer potomania Hypertonic DHN secondary to diarrhea Exogenous salt administration
- 32. DIAGNOSTIC WORKUP Careful historyand examination U/A and microscopy together with plasma electrolytes help exclude most of the causes of polyuria. Water deprivation test Measuring glucose, sodium, and osmolality in urine and serum can quickly distinguish DM, hypertonic DHN, psychogenic polydipsia, and exogenous salt intake from DI.
- 33. DIAGNOSTIC WORKUP Polyuria >2000ml/day Document presence of polyuria (usually 4-15 L/24hrs) Urinary sp. gr. of 1.001-1.005 Increased serum osmolality-Na In a normal well hydrated subject: plasma osmolality is <290 mosml/L and urine osmolality is 300-450 mosmol/L. In patients with DI and free excess to water: plasma osmolality is >295 mosmol/L & urine osmolality is 50-150 mosmol/L.
- 34. WATER DEPRIVATION TEST Water deprivation test is needed for patients with partial AVP deficiency and also to differentiate DI from primary polydipsia. Should be done in the morning under observation In normal subjects: plasma osmolality hardly rises (< 300) but the urine output is reduced and its osmolality rises (800 – 1200) Fluid deprivation test — withhold fluids for 8-12 hours. Weigh patient frequently. Inability to slow down the urinary output and fail to concentrate urine are diagnostic.
- 35. WATER DEPRIVATION TEST Stoptest if patient is tachic or hypotensive Monitor serum and urine osmolality and ADH levels Patients with primary polydipsia start with low normal plasma osmolality (280) but urine/plasma osmolality ratio rises to >2 after DHN. In patients with DI the plasma but not the urine osmolality rises and Urine/Plasma osmolality ratio remains < 1.5. At the end of the test, ADH is given (20 mg DDAV intranasally or 2 mg IM) and fluid intake allowed. Concentration of the diluted urine confirms central DI and failure suggest nephrogenic causes.
- 36. Diagnosis The cardinal diagnosticfeatures are: a high rate of dilute urine flow (urine output >4 mL/kg/hr) clinical signs of DHN (wt loss, hypotension) mild to marked degree of serum hypernatremia (>150 mEq/L) hyperosmolality (>300 mOsm/kg) low urine osmolality (<300 mOsm/kg) and low sp.gr. (<1.010) despite a normal or elevated serum osmolality
- 37. Management Identify treatable causesof DI The DOC for central DI is DDAVP (synthetic ADH) Desmopressin acetate (DDAVP), an ADH analogue, can be given intranasally, SQ, IV, IM or po to stimulate the kidneys to retain water and reverse the polyuria, polydipsia, and hypernatremia.
- 38. Management……. Desmopressin (DDAVP)a synthetic analog is superior to native AVP b/c: it has longer duration of action (8-10 h vs 2-3 h) more potent its antidiuretic activity is 3000 times greater than its presser activity. If renal in origin,—thiazide diuretics, NSAIDs (prostaglandin inhibition) and salt depletion may help. Educate patient about actions of medications, how to administer meds, wear medical alert bracelet.
- 39. TREATMENT OF NEPHROGENICDI Provision of adequate fluids and calorie Low sodium diet Diuretics High dose of DDAVP Correction of underlying cause DRUGS: Indomethacin, Chlorpropramide, Clofibrate and Carbamazepine. Demeclocycline and other tetracyclines cause permanent if subtle nephrogenic DI; be cautious using them for acne during puberty.
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- 41. SIADH Excessive ADH secretion Retainfluids and develop a dilutional hyponatremia known as syndrome of hyponatremia with inappropriate increased secretion of Vasopressin (SIADH) can be identified in an individuals with encephalitis, brain tumors, head trauma, or psychiatric disease.
- 42. SIADH Causes: Disorders of theCNS like head injury, brain surgery, tumor or infections. Many drugs are capable of interfering with free water clearance (lisinopril, vincristine, phenothiazine's, TCAs, carbamazepine, thiazide diuretics and others). can either affect the pituitary or increase sensitivity to renal tubules to ADH. Often non-endocrine in origin — such as bronchogenic carcinoma.
- 43. SIADH Clinical Manifestations Patients presentwith normovolemic hyponatremia, relatively concentrated urine, and normal renal, thyroid, and adrenal function. Symptoms are related to the degree of hyponatremia and how rapid the hyponatremia progressed. symptoms unlikely with a Na >125 mEq/L. Headache, nausea, lethargy, and other CNS findings may occur when sodium falls ≤125 mEq/L.
- 44. SIADH Management: eliminate cause, give diuretics(Lasix), fluid restriction, monitor in put and out put daily wt., lab chemistries Restoration of electrolytes must be gradual May use 3% NaCl in conjunction with Lasix
- 45. SIADH Management SIADH is adiagnosis of exclusion. Other causes of hyponatremia must be ruled out (hyperglycemia, increased serum lipids or protein). A serum osmolality <280mOsm/kg combined with urine osmolality >200mOsm and urine Na+ concentration >20mEq/L are consistent with SIADH. The patient should appear euvolemic. Most cases of SIADH are self-limited, and the mode of mgt is fluid restriction.
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