Major disorders of pituitary gland

1. Emergency Lecture Series
Disorders of the Pituitary
By Ame M. (BSc, MSc in EMCC)

2. Hypothalamus and Pituitary
The hypothalamus-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 the two lobes are distinct structures.

4. 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.

5. Pituitary Gland
1. The anterior 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.Posterior Pituitary/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/Store and releases
Antidiuretic hormone (ADH) also called arginine vasopressin
(AVP) &
regulates water metabolism
Oxytocin
controls
lactation or milk ejection from breasts
uterine contraction

8. Antidiuretic hormone (ADH) or
Arginine Vasopressin (AVP)
 The supraoptic nucleus (SON) is responsible predominantly for the synthesis of
vasopressin which is the ADH.
 ADH is an octapeptide like oxytocin.
 The close structural similarity of vasopressin and oxytocin explains the overlap
of their biological actions.
 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/AVP
Primary effect of ADH
is on the cells of the distal tubules and collecting ducts of the kidney
is 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 reabsorbed.

10. FUNCTION……
Acting on V1-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 ADH SECRETION
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
Ether, Histamine
Opiates, Nicotine
Phenobarbitone

12. ADH SECRETION IS INHIBITED BY:
Alcohol
Oropharyngeal water reflex
β-adrenergic stimulants
Atrial natriuretic factor (ANF)
Phenytoin

13. Disorders of the Posterior Pituitary

14. Outline
Diabetes Insipidus
Definitions
Causes
Types
Ass’t and Dx
Mgt
SIADH
Definitions
Causes
Dx
Mgt

15. Diabetes Insipidus (DI)
Definitions
DI is 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
polydipsia – Excessive thirst (as in cases of diabetes or kidney
dysfunction)
Osmotic diuresis.

16. Diabetes Insipidus (DI)
Diabetes insipidus (DI)
results from a group of disorders in which
absolute or relative deficiency of ADH or
insensitivity to its effects on the renal tubules.
may complicate the course of critically and acutely ill patients and
can result in acute fluid & electrolyte disturbances.

17. DI …
Classification
Different types of DI, each with a different cause.
Neurogenic/Central DI: most common
Nephrogenic DI: second most common
Dipsogenic DI
Gestational DI

18. Neurogenic DI
 more commonly known as central DI,
 also called central or primary pituitary DI.
 caused by a deficiency of Arginine vasopressin(AVP)
AVP also known as ADH.
 is ADH-deficient
 is due to a lack of vasopressin production in the brain or
 is due to failure of the pituitary gland to release adequate ADH.
 secondary to Panhypopituitarism
 is generally caused by destruction of the neurohypophysis, which can result from
genetic defects, tumors, trauma, or infection.
 However, most cases of neurogenic DI are considered idiopathic.
 Because the neurohypophysis is responsible for storing vasopressin, destruction of
this structure results in vasopressin deficiency.

19. Etiology of Central DI
 It occurs when any organic lesion of the hypothalamus, infundibular stem or posterior pituitary
interferes with ADH synthesis, transport or release.
 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 Central DI…..
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 Central DI……
 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
 is characterized 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 Nephrogenic DI
 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 NEPHROGENIC DI
Nephrogenic DI
 is caused by a renal resistance to the effects of vasopressin.
Inherited as an X-linked recessive disorder
chronic renal disease with failure to concentrate urine.
can result from
a genetic condition,
certain medications e.g. lithium and
general anesthetics,
methoxyflurane and demeclocycline or
renal disease.

26. Dipsogenic DI
 results from an abnormality in or damage to the hypothalamus, which
alters the thirst mechanism.
 is due to 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 & increases urine out put.
 The altered thirst mechanism drives the patient to drink large quantities
of fluid.
 In addition, the production of vasopressin is suppressed, which results in
increased urine output.
 Excessive Water Intake (Secondary DI)
 Excessive IV fluid administration
 Psychogenic polydipsia (lesion in thirst center)
 Desmopressin is ineffective, and can lead to fluid overload as the thirst remains.

27. Gestational Diabetes Insipidus (GDI)
is extremely rare,
only occurs during pregnancy.
usually occurs after the 5th month of pregnancy.
usually resolves spontaneously after childbirth.
During pregnancy, the placenta of affected patients produces an
enzyme (vasopressinase ) that destroys vasopressin.
The resulting deficiency of vasopressin causes the classic
symptoms of DI.

28. Regardless of the etiology, in DI the
ability of the body to increase ADH
secretion or respond to ADH is impaired.

29. Clinical Presentation
S/Sx of DHN are present in those patients in whom:
the thirst mechanism has been impaired or
there is inadequate fluid replacement.
In addition, if a hyperosmolar state exists;
intracellular brain volume depletion occurs as water moves from within
the brain cells to the plasma.

30. Clinical Presentation…..
Signs and Symptoms
 ADH Deficiency
 Polydipsia (if alert)
 Polyuria (5-20 L in 24 hours)
 Fluid Volume Deficit
 Orthostatic hypotension
 Weight loss
 Tachycardia
 Decreased CVP, PCWP
 Poor skin turgor
 Dry mucous membranes
 Intracellular Brain Volume
Depletion
 Confusion
 Restlessness
 Lethargy
 Irritability
 Seizures
 Coma

31. Clinical Presentation…….
 Polydipsia, Polyuria (>2 L/m2/day) & 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
secondary to hypernatremia.
these findings correlate with the degree and rapidity of the rise in serum Na.
Typically, symptoms manifest when serum sodium levels exceed 155 mEq/L.

32. COMPLICATIONS
 Untreated DI can produce:
 Hypernatremic DHN & its neurological sequelea
 Growth retardation
 hypovolemia,
 hyperosmolality,
 circulatory collapse,
 loss of consciousness, and
 central nervous system damage.
 These Cxs are most likely if the patient has
an impaired or absent thirst mechanism.
 A prolonged increase in urinary flow (excessive
urine output) may produce:
 chronic complications, such as
bladder distention,
enlarged caliceal,
hydroureter, and
hydronephrosis.
 Cxs may result from an underlying
condition, such as
 a metastatic brain lesion,
 a head trauma, or
 an infection.

33. COMPLICATIONS
decreased bone mineral density at the lumbar spine
and femoral neck in patients with central DI even in those
treated with desmopressin (dDAVP).
Anterior pituitary hormone deficiency, with decreased
release of growth hormone, thyroid stimulating
hormone, and adrenocorticotropic hormone , also may
be present or develop in patients with idiopathic CDI.

34. Differential Diagnosis
Psychogenic polydipsia
Osmotic diuresis
Diabetes mellitus
Beer potomania
Hypertonic DHN secondary to diarrhea
Exogenous salt administration

35. DIAGNOSTIC WORKUP
Careful history and examination
U/A and microscopy
Plasma/serum electrolytes
Water deprivation test (Dehydration test)

36. DIAGNOSTIC WORKUP
Assessment findings
The patient's history shows
an abrupt onset of extreme polyuria (usually 4 to 16 L/day of dilute
urine, but sometimes as much as 30 L/day),
extreme thirst, and
consumption of extraordinarily large volumes of fluid.
The patient may report
weight loss, dizziness, weakness,
constipation, slight to moderate nocturia and,
in severe cases, fatigue from inadequate rest caused by frequent voiding and
excessive thirst.
In children, reports of enuresis, sleep disturbances, irritability, anorexia, and
decreased weight gain and linear growth are common.

37. Assessment findings……
On inspection, you may notice:
signs of DHN, such as
dry skin & mucous membranes, fever, and dyspnea.
colorless and voluminous urine
Palpation may reveal:
poor skin turgor,
tachycardia, and
decreased muscle strength.
Hypotension may be present on BP auscultation.

38. Diagnostic Tests……
 Urinalysis
 Specific gravity,
 Osmolality,
 Glucose,
 Sodium.
 Serum glucose & electrolytes
 Serum Osmolality
 BUN and creatinine
 Water deprivation test (dehydration test)
 U/A and microscopy together with plasma electrolytes help exclude most of the
causes of polyuria.
 Measuring glucose, sodium, and osmolality in urine and serum
 can quickly distinguish DM, hypertonic DHN, psychogenic polydipsia, and exogenous salt
intake from DI.

39. Diagnostic Tests……
Water deprivation test (dehydration test)
 is a simple, reliable way to diagnose DI and
 differentiate vasopressin deficiency from other forms of polyuria.
 It compares urine osmolality after DHN with urine osmolality after vasopressin
administration.
 Fluids are withheld long enough to result in stable hourly urine osmolality values (an hourly
increase of 30 mOsm/kg of water for at least 3 successive hours).
 After the third hour, the patient is given 5 units of aqueous vasopressin.
 Plasma osmolality is determined immediately before vasopressin administration, and urine
osmolality is measured 30 and 60 minutes later.
 In patients with DI, the increase in urine osmolality after vasopressin administration
exceeds 9%.
 Patients with neurogenic DI respond to exogenous vasopressin with decreased urine
output and increased sp.gr.
 Patients with nephrogenic DI show no response to vasopressin.

40. Diagnostic Tests……
In critically ill patient, the Dx:
shouldn't be delayed for more time-consuming tests;
may be based on the following laboratory values:
Serum sodium > 155 mEq/L
Serum osmolality > 300 mOsm/kg/L
Urine osmolality <200 mosm/kg/L
Urine sp.gr. <1.005.
Increased BUN and creatinine (hemoconcentration)

41. Diagnostic….
In a normal well hydrated subject:
plasma osmolality is 275 – 295mosm/L and
urine osmolality is 300-450 mosm/L.
 In patients with DI and free excess to water:
plasma osmolality is >300 mosm/L &
urine osmolality is 50-200 mosm/L.

42. Nephrogenic DI
Patients unable to produce concentrated urine during
fluid restriction.

43. 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.

44. WATER DEPRIVATION TEST
Stop test 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 I.M.) and fluid intake allowed.
Concentration of the diluted urine confirms central DI and
failure suggest nephrogenic causes.

45. Diagnosis
A persistent output of dilute urine and increasing
hemoconcentration is the hallmark of DI.
The cardinal diagnostic features 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)
serum hyperosmolality (>300 mOsm/kg)
low urine osmolality (<200 mOsm/kg) and
low urine sp.gr. (<1.010) despite a normal or elevated serum
osmolality

46. Management
Identify treatable causes of DI
The DOC for central DI is DDAVP
Desmopressin acetate (DDAVP)
is synthetic ADH
is 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.

47. Management…….
 Desmopressin (DDAVP) a synthetic analog is superior to native AVP b/c:
it has longer duration of action (8-10 hrs Vs 2-3 hrs),
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.

48. Principles of Management for DI
DI mgt is directed at correcting
the profound fluid volume deficit and
electrolyte imbalances associated.
If fluid losses are not replaced, hypovolemic shock can rapidly
develop.
In some cases of DI, vasopressin or agents that simulate ADH
release and renal response to ADH are prescribed to treat the
disorder.
Dx & Tx of the causes are priorities.

49. Principles of Management for DI
 Fluid Volume Replacement
 If the patient is alert and the thirst mechanism is not impaired, allow the patient to drink water to
maintain normal serum osmolality.
 In many critically ill patients, this is not possible.
Administer hypotonic volume, such as dextrose 5% in water, quarter-strength or half-
strength saline, IV as prescribed to restore the hypotonic fluid lost through osmotic diuresis.
The administration of N/S to replace volume is usually contraindicated because it presents
an added renal load,
promoting osmotic diuresis and
worsening dehydration.
In severe DI, where large amounts of fluid replacement are required, the IV intake is usually
titrated to urine output; for example, 400 mL of urine output for 1 hour is replaced with 400
mL IV fluid the next hour.
Hypotonic saline solutions are preferred (quarter-strength or half-strength saline).
A good rule of thumb is to reduce serum sodium by 0.5 mEq/L every hour but no more than
12 mEq/L per day.

50. Principles of Management for DI
Monitor fluid status:
Hourly urine outputs along with measurements of urine sp.gr. every 1-2
hrs should be done along with daily weight and strict intake and output.
Monitor for signs of continuing fluid volume deficit.
If the serum Na+ is > 155 mEq/L, rehydration should occur over 48 hrs.
A serum Na+ > 170 necessitates ICU care.
Monitor neurologic status continuously.
An altered level of consciousness indicates intracellular DHN of the brain
and hypovolemia.
Frequent electrolyte monitoring is recommended during the initial
phase of Tx.

51. ADH Administration or Enhancement
 A definitive Dx regarding the type of DI the patient has should be made before Tx;
 inappropriate Tx can exacerbate symptoms and cause water intoxication and, possibly, severe brain
damage.
 Medications may include the following:
 Aqueous vasopressin
 is a replacement agent administered by SQ injection.
 Its duration of action ranges from 3 to 6 hrs.
 This drug is used in the initial mgt of DI after head trauma or a neurosurgical procedure.
 Desmopressin acetate, a synthetic vasopressin analogue,
 affects prolonged antidiuretic activity and has no pressor effects.
 It may be given orally, by nasal spray that's absorbed through mucous membranes, or by SQ or IV injection.
 The duration of action of desmopressin acetate is 8-20 hrs, depending on dosage.
 Chlorpropamide (Diabinese), a sulfonylurea used in patients with DM,
 is also sometimes used to stimulate endogenous release of ADH and
 is effective if some pituitary function is present.
 Nephrogenic DI
 is treated with a low-sodium, high-protein diet and a thiazide diuretic.
 The mild diuretic action reduces blood volume and enhances sodium and water reabsorption in the proximal tubule.

52. ADH Administration or Enhancement….
In central DI,
Desmopressin (DDAVP), an ADH analogue,
is the DOC and is available in subcutaneous, IV, intranasal, and oral
preparations.
acts on the distal tubules and collecting ducts of the kidney to increase water
reabsorption and has very specific actions with little or no ADH-like activity
elsewhere in the body, most notably vasopressor effects that are prominent in
another vasopressin analogue, aqueous AVP.
Vasopressin
is only given IM or IV and is useful only for very short duration in unconscious
patients in whom recovery of ADH secretion is expected.
However, aqueous vasopressin is less specific than DDAVP and can cause
profound vasoconstriction in splanchnic, portal, coronary, cerebral, peripheral,
pulmonary, and intrahepatic vessels—thus it is not preferred for DI therapy in
critically and acutely ill patients unless DDAVP is ineffective.

53. ADH Administration or Enhancement…..
Adjunctive therapy to enhance ADH release includes nonhormonal agents
such as:
chlorpropamide,
carbamazepine,
thiazides, and
NSAIDs.
 If the patient is unconscious,
injectable DDAVP is given IV or IM 1 to 4 μg every 12 hours until therapeutic
goals are achieved, such as a urine output of 2-3 ml/kg/hour, urine sp.gr. 1.010-
1.020 and serum Na 140-145 mEq/l.
 In conscious patients,
the nasal replacement route is given 10 to 20 μg by spray 2 to 3 times a day.

54. ADH Administration or Enhancement…..
 It is important that DDAVP or other ADH analogues not be administrated unless serum Na is at
least above 145 mmol/L, as serious hyponatremia may result.
 Oral formulations of ADH have a slower onset and duration of action and are not useful in acute
situations.
 Major side effects to watch for include:
 headache,
 abdominal cramps, or
 allergic reactions such as facial flushing.
 Monitor for overmedication, which may precipitate hypervolemia.
 S/Sx of fluid volume excess include:
 dyspnea,
 hypertension,
 weight gain, and
 angina.
 Hyponatremia is another serious consequence and if it develops rapidly can cause extreme
cerebral edema and osmotic demyelination syndrome.
 Therefore, close monitoring of serum sodium is necessary.

55. ADH Administration or Enhancement…..
 For nephrogenic DI,
DDAVP intranasal or oral agents may be adminstered or alternative drugs such
as chlorpropamide or NSAIDs (such as indomethacin) may be given.
Volume excess remains a risk from treatment.
 Chlorpropamide, an older antidiabetic agent, may also result in hypoglycemia.
 Provision of adequate fluids and calorie
 Low sodium diet
 Diuretics
 High dose of DDAVP
 Correction of underlying cause
 DRUGS:
 Indomethacin,
 Chlorpropamide,
 Clofibrate and
 Carbamazepine.

56. Nursing interventions
 keeping accurate records of the patient's
hourly fluid intake and urine output,
vital signs, and
daily weight.
 Close monitoring of the urine sp.gr.
 Also monitor serum electrolyte and BUN levels.
 During dehydration testing, watch for signs of hypovolemic shock.
 Monitor BP, pulse rate, and body weight.
 Also watch for changes in mental or neurologic status.
 instituting safety precautions to help prevent injury,
if the patient has complaints of dizziness or muscle weakness.
 Make sure that the patient has easy access to the bathroom or a bedpan.

57. Nursing interventions
 Provide meticulous skin and mouth care.
 Use a soft toothbrush and mild mouthwash to avoid trauma to the oral mucosa.
 If the patient has cracked or sore lips, apply petroleum jelly as needed.
 Use alcohol-free skin care products, and apply emollient lotion to the patient's skin after baths.
 Use caution when administering vasopressin to a patient with coronary artery disease because
the drug can cause coronary artery constriction.
 Closely monitor the patient's ECG, looking for changes and exacerbation of angina.
 Urge the patient to verbalize feelings.
 Offer encouragement, and provide a realistic ass’t of the situation.
 Help the patient identify his strengths, and help him see how he can use these strengths to
develop effective coping strategies.
 As necessary, refer the patient to a mental health professional for additional counseling.
 Advise the patient to wear a medical identification bracelet at all times.
 Tell him he should also always keep his medication with him.

58. ?

59.  ADH exerts its primary effects in the distal collecting tubules of the kidneys
where it decreases water excretion, conserving body water, thereby increasing
urine concentration (osmolality) and hemodilution.
 Osmoreceptors in the hypothalamus monitor changes in blood osmolality.
 An increase of osmolality by 2% leads to ADH release by the posterior
pituitary.
 In high conc., usually via exogenous administration, ADH has potent
vasopressor effects along with pro-coagulant (platelet aggregation) properties.
Syndrome of Inappropriate ADH Secretion

60. Etiology, Risk Factors, and Pathophysiology
The SIADH and DI are the most common disorders associated
with ADH secretion in the critically ill.
The SIADH is char’zed by
excessive release of ADH unrelated to the plasma osmolality, or the
conc. of electrolytes and other osmotically active particles.
Normal mechanisms that control ADH secretion fail, causing
impaired water excretion and
profound hyponatremia.
SIADH is a syndrome of water intoxication.

61. Etiology, Risk Factors, and Pathophysiology
 Vasopressin can be produced by a variety of malignancies, most commonly oat cell carcinoma
of the lung.
 Therefore, patients who develop “idiopathic” SIADH are screened for malignant tumors.
 SIADH is also commonly associated with:
 pulmonary conditions,
 metabolic and traumatic CNS disorders, and
 drugs, particularly
 chlorpropamide,
 thiazide diuretics,
 opiates, and
 barbiturates.
 Surgical patients are also at risk because of
 increased vasopressin secretion due to
 perioperative surgical stress and t
 he use of opiate analgesics such as morphine.
 Clinically, SIADH is distinguished by hyponatremia and water retention that progresses to
water intoxication.

62. Etiology, Risk Factors, and Pathophysiology
 The seriousness of the patient’s S/Sx depends on how fast the serum sodium falls.
 As water intoxication progresses and the serum becomes more hypotonic, brain cells
swell, causing neurologic impairment.
 Without Tx, irreversible brain damage and death can occur.
 Excessive ADH secretion
 Retain fluids and develop a dilutional hyponatremia known as syndrome of
hyponatremia with inappropriate increased secretion of Vasopressin (SIADH)
 There are many causes of SIADH.
 can be identified in an individuals with
 encephalitis,
 brain tumors,
 head trauma, or
 psychiatric disease.

63. Etiology, Risk Factors, and Pathophysiology
ETIOLOGY
One of the following causes of persistent ADH release is likely to be
present in patients who fulfill the clinical criteria for the SIADH:
CNS disturbances
Any CNS disorder, including stroke, hemorrhage, infection, trauma, and
psychosis, can enhance ADH release.
hyponatremia associated with intracranial bleeding, as well as ther
severe neurologic events, is due to
ADH-mediated water retention and
urinary sodium losses.

64. Etiology, Risk Factors, and Pathophysiology
Malignancies
Ectopic production of ADH by a tumor
is most often due to a small cell carcinoma of the lung and
is rarely seen with other lung tumors.
Less common causes of malignancy-associated SIADH
include:
head and neck cancer,
olfactory neuroblastoma (esthesioneuroblastoma), and
extrapulmonary small cell carcinomas.

65. Etiology, Risk Factors, and Pathophysiology
Drugs
Certain drugs can enhance ADH release or effect, including:
chlorpropamide , carbamazepine , oxcarbazepine (a derivative of carbamazepine),
high-dose IV cyclophosphamide , and
selective serotonin reuptake inhibitors. (e.g., fluoxetine , sertraline ).
Many other drugs have been associated with the SIADH.
These include vincristine , vinblastine , vinorelbine , cisplatin , thiothixene ,
thioridazine , haloperidol , amitriptyline , monoamine oxidase inhibitors,
melphalan , ifosfamide , methotrexate , opiates, nonsteroidal antiinflammatory
agents, interferon-alpha, interferon-gamma, sodium valproate , bromocriptine ,
lorcainide, amiodarone , ciprofloxacin , high-dose imatinib , and "ecstasy"
(methylenedioxymethamphetamine), a drug of abuse that may also be
associated with excessive water intake.

66. Etiology, Risk Factors, and Pathophysiology
Surgery
Surgical procedures are often associated with hypersecretion of ADH, a
response that is probably mediated by pain afferents.
hyponatremia may develop after other types of interventional procedures,
such as cardiac catheterization.
Rarely, hyponatremia after pituitary surgery is due to cerebral salt
wasting.
Pulmonary disease
particularly pneumonia (viral, bacterial, tuberculous), can lead to the
SIADH, although the mechanism is not clear.
infrequently seen with asthma, atelectasis, acute respiratory failure, and
pneumothorax.

67. Etiology, Risk Factors, and Pathophysiology
Hormone deficiency
Both hypopituitarism and hypothyroidism may be associated with
hyponatremia and an SIADH picture that can be corrected by hormone
replacement.
Hormone administration
The SIADH can be induced by exogenous hormone administration, as with
vasopressin (to control gastrointestinal bleeding),
desmopressin (dDAVP, to treat Von Willebrand disease or hemophilia
or platelet dysfunction), or
oxytocin (to induce labor).
As with vasopressin and desmopressin, oxytocin acts by increasing the
activity of the V2 (antidiuretic) vasopressin receptor.

68. Etiology, Risk Factors, and Pathophysiology
HIV infection
A common cause of hyponatremia is symptomatic HIV
infection, either AIDS or early symptomatic HIV infection.
Although volume depletion (due, for example, to GIT losses)
or adrenal insufficiency may be responsible, many patients
have the SIADH.
Pneumonia, due to Pneumocystis carinii or other organisms,
CNS infections, and malignant disease, are most often
responsible in this setting.

69. Etiology, Risk Factors, and Pathophysiology
Hereditary SIADH
genetic disorders that result in antidiuresis.
two genetic abnormalities have been identified,
one affecting the gene for the renal vasopressin-2 (V2) receptor, and
one affecting osmolality sensing in the hypothalamus.
Idiopathic
Idiopathic SIADH has been described primarily in elderly patients.
However, some cases of apparently idiopathic disease were later found to
be caused by an occult tumor (most often small cell carcinoma or olfactory
neuroblastoma) and, in older patients, giant cell (temporal) arteritis.

70. Etiology, Risk Factors, and Pathophysiology
CEREBRAL SALT WASTING
A rare syndrome has been described in patients with cerebral
disease (particularly SAH) that mimics all of the findings in the
SIADH except that salt wasting is thought to be the primary
defect, with the ensuing volume depletion causing a secondary
rise in ADH release.

71. Etiology, Risk Factors, and Pathophysiology
Among patients with SIADH, the combination of water retention
and secondary solute (Na+ plus K+) loss accounts for
essentially all of the reduction in serum sodium.
Hyponatremia
is initially mediated by ADH-induced water retention.
may also be associated with potassium loss.
Since potassium is as osmotically active as sodium, the loss of
potassium contributes to the reductions in plasma osmolality
and sodium concentration.

72. ETIOLOGIES OF SIADH (PARTIAL LISTING)
 Malignancies
 Lung
 Lymphoma
 Gastrointestine
 Often non-endocrine in origin — such as bronchogenic
carcinoma.
 Pulmonary Diseases/Conditions
 Positive pressure ventilation
 Asthma
 Pneumonia
 COPD
 Acute respiratory failure
 Tuberculosis
 CNS Disorders
 Head injury, Brain surgery,
 Infections (Meningitis, encephalitis)
 Cerebrovascular accidents
 Brain tumors
 Guillain-Barré syndrome
 Drugs
 Many drugs are capable of interfering with free
water clearance
 can either affect the pituitary or increase sensitivity
to renal tubules to ADH.
 Vasopressin, Desmopressin
 Phenothiazine's, Carbamazepine,
 Thiazide diuretics
 Narcotics, Nicotine, Barbiturates
 Antineoplastic drugs
 Tricyclic antidepressants
 Others
 AIDS
 Senile atrophy

73. Clinical Presentation
 Early
 Urine volume decreased and concentrated
 Nausea, Vomiting
 Headache
 Impaired taste
 Dulled sensorium
 Muscle weakness and cramps
 Anorexia
 Weight gain
 Crackles
 Dyspnea
 Increased CVP, PCWP
 Weakness/fatigue
 Late
Confusion
Hostility
Aberrant respirations
Hypothermia
Coma
Convulsions
Signs and Symptoms

74. Clinical Presentation……
Patients with normovolemic hyponatremia present with,
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.

75. Clinical Presentation……
In acute hyponatremia;
the severity of symptoms generally reflects
the severity of cerebral overhydration, which is related to the degree of hyponatremia.
The major clinical manifestations of acute hyponatremia include :
Nausea and malaise, which are the earliest findings,
may be seen when the serum Na+ conc. falls below 125 to 130 mEq/L
 if the serum sodium conc. falls below 115 to 120 mEq/L:
 Headache, lethargy, obtundation and eventually seizures, coma, and respiratory arrest
can occur.
 Noncardiogenic pulmonary edema has also been described.
 Acute hyponatremic encephalopathy can occur
 Overly rapid correction also may be deleterious, particularly in patients with
chronic hyponatremia.

76. Diagnostic Tests
 Blood chemistries
U/A
 BUN and creatinine
 Serum Na+ < 135 mEq/L
 Serum osmolality < 275 mosm/kg
 Increased urine osmolality > 500 mosm/kg
 Urine Na+ > 20 mEq/L
 BUN and creatinine decreased (hemodilution)
 A serum osmolality <275 mosm/kg combined with urine osmolality >200
mosm and urine Na+ conc. >20mEq/L are consistent with SIADH.

77. Principles of Management for SIADH
Principles of mgt depend on the
severity & duration of the hyponatremia.
Hyponatremia in the SIADH results from ADH-induced retention of
ingested or infused water.
Although water excretion is impaired, Na+ handling is intact, since there
is no abnormality in volume-regulating mechanisms such as
the renin-angiotensin-aldosterone system or atrial natriuretic peptide.
early recognition is key to prevent life-threatening cxns.
Continued ass’t of neuromuscular, cardiac, GI, and renal systems is
important.

78. Principles of Management for SIADH
The choice of therapy of SIADH is dependent upon a number
of factors including:
the degree of hyponatremia,
the presence or absence of symptoms, and,
the urine osmolality (to some degree)
Generally, Tx focuses on:
restricting fluids,
replenishing sodium deficits, and
inhibiting antidiuretic actions – in severe cases of hyponatremia,.
Tx of the underlying disorder is also a priority.

79. THERAPIES TO RAISE THE SERUM SODIUM
A number of modalities can be used to correct hyponatremia in the
SIADH,
most importants are:
fluid restriction,
salt administration, and
vasopressin receptor antagonists.
When treating such patients, attention must be paid to the rate of
correction.
There are three components to the Tx of hyponatremia in SIADH:
Treatment of the underlying disease, if possible
Initial therapy to raise the serum sodium
Prolonged therapy in patients with persistent SIADH

80. Treat the underlying disease
 SIADH is a Dx of exclusion.
 Eliminate the cause.
 Other causes of hyponatremia
must be ruled out
 hyperglycemia, increased serum
lipids or protein.
 A variety of causes of SIADH
can be effectively treated, leading
to resolution of the hyponatremia.
These include:
Hormone replacement in
adrenal insufficiency or
hypothyroidism
Treatment of infections such as
meningitis, pneumonia, or tuberculosis
Cessation of offending drugs, such
as
Selective serotonin reuptake inhibitors or
Chlorpropamide

81. Fluid Restriction
is the mainstay of Tx.
is a standard component of therapy in SIADH,
but may promote cerebral vasospasm in patients with SAH who
are usually treated with volume expansion.
Tx of mild hyponatremia (Na+ level 125 – 135 mEq/L) includes
fluid restriction of 800 to 1000 mL/d.
this allows Na+ level to correct over 3 to 10 days.

82. Intravenous saline
Severe, symptomatic, or resistant hyponatremia in patients
with SIADH often requires the administration of NaCl.
isotonic saline has no role in symptomatic hyponatremia due
to SIADH.
If the serum Na+ conc. is to be elevated, the electrolyte conc.
of the fluid given must exceed the electrolyte conc. of the
urine, not simply that of the plasma.

83. Replenish Sodium Deficits
 3% saline infusion over 2-3 hrs, if;
 severe symptomatic hyponatremia of SIADH
 severe neurologic symptoms of SIADH are present along with severe
hyponatremia (< 125 mEq/L).
hyponatremic patients present with SAH
to preserve cerebral perfusion and
to prevent cxns from hyponatremia-induced brain swelling.
infuse 3% saline at a rate of 0.1 mL/kg/min for 2 hrs to raise plasma Na+.
 b/c this Tx causes a transient increase in the serum Na+:
Monitor closely for signs of:
hypernatremia,
fluid overload, and
heart failure.

84. Inhibit ADH Actions
 Drugs that interfere with the renal effect of ADH are used:
 If fluid restriction alone is not effective, or
 In cases where SIADH does not resolve within 1 to 2 weeks.
e.g. demeclocycline can be administered.
Demeclocycline and lithium
 act on the collecting cell of the renal tubules,
 to diminish its responsiveness to ADH, or
 inhibits the effect of ADH on the renal tubules,
 thereby increasing water excretion.
 these drugs are not suitable for acute mgt of the syndrome
 due to their full effects.

85. High solute intake
 a high salt and protein diet without a increase in water ingestion.
is one way to increase water excretion in patient with SIADH.
 The increase in water excretion would then tend to raise the plasma
Na+ conc. toward normal.
 high solute diet can be combined with a loop diuretic, which interferes
with concentrating ability and lowers the urine osmolality.
 These includes:
Oral salt tablets
Salt plus a loop diuretic
Urea

86. High solute intake
 Oral salt tablets
sodium chloride in tablet form
 Some patients with chronic SIADH have a major underlying illness (such as small
cell carcinoma) that may limit compliance with increased dietary salt intake.
 Salt plus a loop diuretic
 The effect of salt tablets can be enhanced if given with a drug that
lowers the urine osmolality and
increases water excretion.
This can be achieved by
impairing the renal responsiveness to ADH by the administration of
a loop diuretic or
a vasopressin receptor antagonist.

87. High solute intake
Loop diuretics
 e.g., furosemide 20 mg orally twice a day
 directly interferes with the countercurrent concentrating mechanism by
decreasing NaCl reabsorption in the medullary aspect of the loop of Henle.
 will be effective if the Uosm is more than twice the Posm, which typically means a Uosm
above 500 mosm/kg.
 Monitoring of the serum K+ is important, particularly in the early stages of therapy.
 Some patients require
 KCL supplementation or
use of a potassium-sparing diuretic, such as amiloride .
 Urea
 increase urinary solute excretion and
 enhance water excretion
 usual dose is 30 g/day.

88. Vasopressin receptor antagonists
 There are three receptors for vasopressin (ADH):
 the V2 receptors – primarily mediate the antidiuretic response,
 the V1a & V1b receptors – primarily cause vasoconstriction & ACTH release,
respectively.
 The vasopressin receptor antagonists produce:
 a selective water diuresis (aquaresis) without affecting Na+ and K+ excretion.
 The ensuing loss of electrolyte-free water will tend to:
 raise the serum Na+ in patients with SIADH and
 Some oral formulations selective for the V2 receptor are:
 tolvaptan , mozavaptan, satavaptan, and lixivaptan,
 while an IV agent, conivaptan , blocks both the V2 and V1a receptors.

89. RATE OF CORRECTION
the initial rate of correction is determined by:
the severity of neurologic symptoms attributable to hyponatremia.
in patients with severe symptoms (e.g., seizures).
initial rate of correction of 4 to 6 mEq/L in the first 2 to 4 hrs may be beneficial
this requires careful monitoring of the serum Na+ conc.
initially every 2 to 3 hrs until the patient is stable.
 the maximum rate of correction of chronic hyponatremia should be <9
mEq/L in any 24-hr period.

90. CHOICE OF THERAPY
Choice of therapy Varies:
with the severity of hyponatremia and
the presence or absence of symptoms.
Symptomatic hyponatremia
approach varies with the severity of the neurologic symptoms.

91. Severe symptoms of hyponatremia
 e.g., seizures, inability to communicate, and/or coma
 are most likely to occur when serum Na+ <120 mEq/L in <48 hrs, leading to
potentially fatal cerebral edema.
 the administration of hypertonic saline (3 %)
is the only rapid way to
raise the serum Na+ and
improve neurologic manifestations.
 The rise in serum Na+ will pull water out of the brain, decreasing the degree
of cerebral edema.
 If neurologic symptoms persist or worsen, a 100 mL bolus of 3 % saline can
be rptd one or two more times at 10 min intervals.
 Rationale for this approach is that,
in patients with symptomatic hyponatremia, rapid increases in serum sodium of 4
to 6 mEq/L can reverse severe symptoms such as seizures.

92. Severe symptoms…..
If the symptoms resolve, careful monitoring with measurement of the
serum Na+ conc. every 2 to 3 hrs is required for two reasons:
A potential cxns of hypertonic saline therapy is overly rapid correction
of the hyponatremia,
The usual goals are an elevation in serum Na+ of <10 meq/L in the first
24 hrs and <18 meq/L in the first 48 hrs.
In patients with severe hyponatremia who are correcting too rapidly,
prevention of further short-term elevation in the serum Na+ or even
relowering of the serum Na+ may be warranted.

93. Mild to moderate symptoms of Hyponatremia
 Less severe neurologic symptoms (e.g., dizziness, gait disturbances, forgetfulness,
confusion, and lethargy) can be seen:
 in patients with a serum Na+ conc. <120 mEq/L that develops over more than 48 hrs,
 in patients with a lesser degree of hyponatremia that develops over <48 hrs, and
 in patients with chronic moderate hyponatremia (serum Na+ 120 – 129 mEq/L).
 Some of these patients may benefit from hypertonic saline, but do not require the
aggressive approach suggested for those with severe neurologic symptoms.
 Initial hypertonic saline therapy to raise the serum Na+ at rates up to 1 mEq/L per hr
may be justified in the first 3 to 4 hrs in patients with distressing symptoms (e.g.,
confusion and lethargy).
 The total elevation in serum Na+ in the first 24 hrs should be <10 mEq/L.
 Patients with less severe symptoms
 can be treated with less aggressive therapy, such as
fluid restriction and oral salt tablets.

94. Maintenance therapy
 Unless the SIADH is reversible (e.g., postoperative or due to a drug that can be discontinued), effective
therapy of symptomatic hyponatremia must be followed by maintenance therapy to prevent a subsequent
reduction in serum Na+ and possible symptom recurrence.
 One or more therapeutic modalities may be required.
 The usual sequence of maintenance therapy is as follows:
 Fluid restriction
The suggested goal fluid intake in hyponatremic patients with SIADH is <800 mL/day.
An important exception is patients with a recent SAH in whom fluid restriction can be deleterious.
 Oral salt –
In patients with SIADH, administering oral salt will increase the urine output;
the usual initial dose is 3 g or one-half teaspoon three times daily, resulting in a total dose of 9 g per
day.
Since sodium handling is normal and the urine osmolality is relatively fixed in SIADH, increasing oral
salt intake will, in a dose-dependent fashion, increase the urine volume.
 Reduce the urine osmolality
to increase urinary water excretion by impairing the mechanism of urinary concentration.
can be achieved by loop diuretic therapy (e.g., furosemide 20 mg orally twice a day).

95. Goal of serum sodium
 130 mEq/L or higher in patients with SIADH b/c of
the possible presence of subtle neurologic manifestations and falls when
the serum Na+ is b/n 120 and 129 mEq/L.
 serum Na+ of 130 mEq/L or higher can be attained in almost all patients
with SIADH with:
fluid restriction,
oral salt tablets alone or
a loop diuretic, and,
Urea – If necessary and where available.

96. Nursing Intervention
 Monitoring neurologic status closely and protect the patient from harm.
 Institute seizure precautions as necessary.
 Monitoring respiratory status closely.
 Monitoring closely for signs of:
 hypernatremia,
 fluid overload, and
 heart failure.
 Assess cardiovascular and respiratory functions closely to evaluate the effects of the excess
volume on these systems.
 Right and left ventricular volumes may increase, causing heart failure.
 Indicators of fluid overload and impending heart failure are:
Tachypnea, reports of SOB, and fine crackles
 Provide for patient comfort with limited fluid intake.
 Provide for frequent mouth care.
 Explain why fluid is being restricted and allow the patient to develop the schedule for allotted fluid
intake.
 If the patient complains of nausea, administer an antiemetic prior to meals.

97. Summary
Choice of therapy Varies:
with the severity of hyponatremia and
the presence or absence of symptoms.
Management of SIADH:
eliminate cause,
fluid restriction,
give diuretics (Lasix),
monitor in put and out put
daily wt.,
Restoration of electrolytes must be gradual
May use 3% NaCl in conjunction with Lasix

98. The END