Diseases of Posterior Pituitary

Hasan AYDIN, MDYeditepe University Medical Faculty

Department of Endocrinology and Metabolism

Posterior PituitaryPosterior pituitary

(neurohypophysis)

It is continuous with the brain

Formed during embryonic development from an outgrowth of the inferior part of the brain in the area of the hypothalamus

Secretions of the posterior pituitary are considered as neurohormones

Antidiuretic Hormone (ADH)

Named so because it prevents the output of large amounts of urine

Constricts blood vessels and raises blood pressure when large amounts of urine are released

Its primary target tissue is the kidneys, where it promotes the retention of water, and reduces urine volume

Urine volume increases within minutes to a few hours in response to increased water intake, and decreases if water is not consumed.

1 % increase in osmolality (3 mOsm/kg

H2O) stimulates ADH secretion.

Serum osmolality above 290 mOsm/kg H2O (N:

285 mOsm/kg H2O) stimulates thirst center.

The actions of ADH is mediated by G-protein coupled cell surface receptors V1, V2, V3

Antidiuretic Hormone (ADH)

V1 Receptors

Located onVascular smooth muscle cellsLiverThrombocytesRenal medulla, hypocampus, amygdala, hypothalamus and brain stem

When stimulated causesVasoconstrictionGlycogenolysisThrombocyte aggregation

V2 Receptors

Found on renal distal tubular and collecting duct cells

V2 receptor gene is on short arm of X chromosome (Xq28).

Mutations cause congenital X-linked Nephrogenic DI

V3 Receptors

Found on ACTH secreting cells of anterior hypophysis

Activation with ADH causes ACTH release

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 (nausea, hypoglycemia, hypoxia, acidosis)

Other ADH Stimulants

Cholinergic stimulation Αlpha-adrenergic stimulation Angiotensin II Prostoglandin E Opiates Nicotine Histamine Ether Phenobarbitone

ADH Secretion is Inhibited by:

Alcohol

Oropharengeal water reflex

β-adrenergic stimulants

Atrial natriuretic factors (ANF)

Phenytoin

Actions of ADH

Functions of ADH

• Primary Effect

– Water reabsorbtion from the distal tubules and collecting ducts of the kidney

– Mediated by V2 receptors through the activation of cAMP and formation of a spesific protein known as “AQUAPORIN”

Aquaporins

Actions of ADH

• During hypovolemia plasma levels of ADH maintain tissue perfusion

• Via V2 stimulates synthesis and release of factor VIII & Von Willebrand factor

Pathological States

Disorders/diseases resulting from dysfunction

– Excess: Syndrome of Inappropriate ADH secretion (SIADH)

– Deficiency: Diabetes Insipidus

DIABETES INSIPIDUS

Diabetes Insipidus

• Syndrome of posterior pituitary hypofunction

• S/S– Increased thirst - polydipsia– Increased urination - polyruia

• Results from – ADH (Vasopression) deficiency, which prevents the

kidneys from reabsorbing water– Inability to conserve water

Types of Diabetes Insipitus

– Cental Diabetes Insipidus

– Nephrogenic Diabetes Insipidus

– Dispogenic Diabetes Insipidus

– Gestational Diabetes Insipidus

Central Diabetes Insipitus (Neurogenic DI)

• Results from damage to the pituitary gland

• Results in a deficiency of antidiuretic hormone (ADH).

Nephrogenic Diabetes Insipitus

• Vasopressin-resistant.

– Caused by insensitivity or inability of the

kidneys to the effect of ADH.

– Can be caused by

• Certain drugs such as lithium

• Blockade of the ureters

• Genetic disorders (Mutations in the aquaporin-2 gene

)

Dipsogenic DI (primary polydipsia)

• Occurs when vasopressin is suppressed by excessive intake of fluids

• Most often caused by an abnormality in the part of the brain that regulates thirst

• Primary polydipsia is due not to abnormal thirst but to psychosomatic causes

Gestational DI

• Occurs during pregnancy

• An enzyme made by the placenta destroys ADH in the mother

• DI often disappear 4 to 6 weeks after delivery

• Often recur with subsequent pregnancies

Causes of Diabetes Insipitus

Causes of Central Diabetes Insipidus

• Hypophysectomy, complete or partial • Surgery to remove suprasellar tumors • Idiopathic • Familial • Tumors and cysts (intra- and suprasellar) • Histiocytosis • Granulomas • Infections • Interruption of blood supply • Autoimmune

Causes of Nephrogenic Diabetes Insipidus

• Chronic renal disease• Hypokalemia • Protein starvation • Hypercalcemia • Sickle cell anemia • Sjögren's syndrome • Drugs, eg, lithium, fluoride, methoxyflurane

anesthesia, demeclocycline, colchicine, foscarnet, cidofovir

• Congenital defect • Familial

Clinical Features

• Poliuria, polydipsia & thirst

• Nocturia or nocturnal enuresis

• Hypernatremic dehydration

• Anorexia, constipation

• Hyperthermia and lack of sweating

• Symptoms of underlying cause

Diagnostic Work-up

• Document presence of polyuria (usually 4-5 L/24 hours)

• Measurement of plasma and urine osmolality

• In DI– Plasma osmolality >295 mOsmol/l – Urine osmolality 50-150 mOsmol/l

Water Deprivation Test

• Useful in patients with partial ADH deficiency

• Differentiate DI from primary polydipsia

Water Deprivation Test

• Should be done in the morning under supervision

• Weigh hourly and measure plasma and urine osmolality every 2 hours

• In pts with DI plasma but not urine osmolality rises, U/P osm ratio < 1.5

• Testing can proceed if urinary osmolality stabilized for 3 samples and 3% wt loss is noted

• At the end of the test ADH given (20 mg DDAVP intranasally or 2 mg im) and fluid intake allowed

• Concentration of dilute urine confirms central DI and failure suggests nephrogenic causes

Differential Diagnosis

• Psychogenic polidipsia

• Medullary cystic disease

• Drugs (Lithium, diuretics)

• Osmotic diuresis (DM)

• Hypercalcemia, hypokalemia

• Postobstructive diuresis (pyelonefritis, renal tubular acidosis, sickle cell anemia)

• Hyperthyroidism

Treatment

• Desmopressin (DDAVP): – A synthetic analogue – Longer duration of action (8-10 h vs 2-3 h)– More potent – ADH activity 3000 x greater than pressor

activity– Usually given intranasally but sc and oral

administration possible

Treatment of Nephrogenic DI

• Provision of adequate fluids and calorie• Low sodium diet• Diuretics• High dose of DDAVP• Correction of underlying cause• Drugs (Indomethacin, Chlorprooramide,

Clofibrate & Carbamazepine)

Syndrome of Inapproriate Secretion of ADH

(Posterior Pituitary Hypersecretion)

SIADH occurs:

• When there is too much

vasopression (ADH) with

inappropriate water retention

and decreased blood Na levels

Syndrome of Inappropriate Antidiuretic Hormone

Secretion - SIADH

• Results from– Inability to produce & secrete dilute urine– Water retention– Increased extra cellular fluid volume– Hyponatremia – Diseases that affect the hypothalamus

Etiology

• 1.Central Nervous System Diseases

– Menengitis, Ensephalitis, Abcess, Trauma,

– Hypoxic ischemic state, Tumor,

– Guillain Barre Syndrome,

– Ventriculo- atrial shant obstruction,

– Acute intermittant porfiria,

– Sinus thrombosis,

– Hemorrhagia (Intracerebral, subarachnoid).

2. Respiratory system diseasesPneumonia, aspergillosis, tbc, Positive pressure ventilation, Pneumotorax, atelectasia, astma,

cystic fibrosis, 3. Malignancy,

Thymoma, Lymphoma, Ewing sarcoma, Duedonum, Pancreas, Ureter, Prostate,

Baldder and Bronchogenic carcinoma,4. Drugs eg. vincristin,5. Myxedema6. Idiopathic.

SIADH

Increased secretion of AVP causes euvolemic hyponatremia. This causes abnormal thirst and intake of excess water leading to accumulation of water and at the end dilutional hyponatremia.

As a result, serum Na decreased. urinary excreation of Na increased. urine density and osmolality increased.

Clinical Findings

• Anorexia, apathy, confusion, headache,

weakness, cramps in abdominal and

extremity muscles , nausea, vomiting,

abdominal floating

• Neurological signs include slowness in

DTR, pathological reflexes, in severe

cases convulsions and coma.

Dx of SIADH

• The following criteria should be fulfilled before a diagnosis of SIADH can be made:

– persistent excretion of concentrated urine with no reason for ADH release

– normal renal and adrenal function

– no edema or hypovolaemia should be present

– the urine osmolarity should be greater than the serum osmolarity

Lab Assessment in SIADH

• Elevated urine sodium levels and specific gravity reflect an increased concentration of the urine

• Serum sodium levels are decreased, often as low as 110 mEq/L (normal serum sodium 135-145 mEq/L) due to extracellular volume expansion and increased Na excretion

• Fluid retention causes changes in both plasma and urine osmolality

• Plasma osmolality is decreased, and the urine is hyperosmolar in relation to the plasma

SIADH Treatment

• Water Restriction is the cornerstone of treatment

• Decreased water intake allows serum sodium level to rise normally.

• The maximum amount of water that pt with SIADH are allowed to drink is just slightly more that the amount of urine they produce

• Pt must have regular serum sodium measurements to ensure that the water restriction has been effective

• Dehydration- The most concerning potential side effect from treatment is dehydration.

SIADH Treatment

• Restrict fluid intake (800-1000 cc/day)• Daily weight Strict I & O• Monitor urine specific gravity• 0.9 NS infusion(to raise the serum Na level if water

intoxication is severe)

• Monitor for hyponatremia • Furosemide may be admin to block circulatory

overload• Drugs-demeclocyclin HCL & lithium-may be admin to

block renal response to ADH, intereferes with action of ADH

• Drugs - Phenytoin - inhibits ADH release

• Surgery & Chemo -to remove or destroy neoplasms that may be the underlying cause of this syndrome

SIADH Treatment• Demeclocycline (Declomycin)• Lithium

• Used for:– Excess secretion of ADH or SIADH

• Action:– Inhibits ADH action in kidney– Blocks renal response to ADH, interferes with action

of ADH

• Therapeutic outcome:– Decreased urine specific gravity