Diabetes Insipidus

Dr Thomas Fox

Endocrine SpR RCH

Diabetes from the Greek diabainein – To stand with the legs apart

Insipudus meaning lack of taste

Outline

Anatomy of posterior pituitary Water physiology and anti-diuretic

hormone (arginine vasopressin) Clinical cases Investigations and differential diagnoses Management Conclusions

Anti-diuretic hormone (Arginine Vasopressin )

Anti-diuretic hormone (ADH) Molecular weight 1084 Polypeptide hormone Produced

– from prohormone neurophysin II– by the macrocellular neurons– In the suprasellar nucleus

Released in the posterior PituitaryHepatic metabolismHalf life 10-20mins

                                                                                         

Water homeostasis

Intake– 1.2 litres daily from food/metabolism– 1-2 litres daily water intake

Output– Stool– Insensible losses skin, lungs etc)– Urine

Role of ADH

To maintain euvolaemia– Water intake

• Stimulated by hypertonic saline and sucrose but not hypertonic urea

– Water excretion– Vascular resistance

H20H20

Collecting Duct

Principal cell

ADH

DNA

AQP 2

Synthesis

Transport

AQP 2

ADH affect on kidney

V2 R

ADH production

In response to increased osmolality– Increased osmolality– Cellular dehydration via auaporins in

hypothalamic osmoceptors– Linear response with increasing osmolality

ADH Production in response to volume and osmolality changes

ADH Production

In response to reduced reduced extracellular volume– Stimulate baroreceptors in jugular vein– Need a large volume loss to stimulate ADH

production– Acts via V1 receptors in vascular systems

Case 1

Initial referral 1999 18y/o male with 3 month history of

– dry mouth, thirst– Dinking 10 litres fluid per day– Nocturia 3-4 nightly– No weight loss

PMHx nil DHx nil SHx drinks 4-5 unites EtOH weekly

Case cont

Examination normal Biochemistry

– Na 136 mmol/L– K 4.1 mmol/L – Urea 3.3 mmol/L– Creatinine 85 uimol/L– C ca 2.28 mmol/L– Plasma glucose 7.3 mmol/L– Plasma osmolarity 284 mmol/kg– Urine osmolarity 84 mmol/kg

Impression– Biochemistry consistent with psychogenic

polydipsia

Pt reviewed 6/12 later– Feeling better – Still thirsty all the time but drinking less in

total– discharged

2 years later

Routine contact lens F/U with optician– Pt described reduced vision– Had bitemporal hemianopia

GP referred the patient to neurology who arranged MRI brain

MRI abnormal so patient referred for acute admission

On admission

Na 146 mmol/L K 4.8 mmol/L LH and FSH <0.9 IU/L Testosterone <0.9 mmol/L Cortisol 15 nmol/L, ACTH <10 ng/L PRL 1148 miU/L TSH 5.4 miU/L FT4 4.9 pmol/L, FT3 4.5 pmol/L ILGF-1 12.5 nmol/L

synACTHen, GnRH and TRH tests normal response to stimulation

MRI brain showed;

An irregular enhancing suprasellar mass in the region of the hypothalamus and floor of the third ventricle, immediately abutting the optic chiasm.

There wass a further 2.2cm mass seen at the scene in the posterior 3rd ventricle immediately adjacent to the tectum and aqueduct

Appearances consistent with glioblastoma, no evidence of hydrocephalus

Treatment - medical

Dexamethasone 0.5/0.25mg daily Levothyroxine 100mcg od Sustanon 250 every 3 weeks Desmopressin 20mcg nasally od

– serum osmolality 300mosm/L (pt chooses not to take 2nd dose of desmopressin)

Treatment – surgical

Biopsy confirmed a germinoma Ommaya shunt sited

Subsequently treated with craniospinal radiotherapy

Case 2

64 year-old female– PMHx

• Osteoarthritis• Essential hypertension• Fibromyalgia• Previous gallstone pancreatitis• Laparoscopic cholecystectomy

Referred by rheumatology consultant with severe polydipsia, polyuria and nocturia– Drinking 6-8litres daily– Passing 7 litres urine daily– Nocturia 2-3 times

DHx– Irbesartan 300mg– Diltiazem MR 300mg– Amitriptyllijne 10mg– Tramadol MR 400mg– Co-codamol

On examination– Not dehydrated– No visual field defect– BP 152/94

Biochemistry– Cor Ca 2.61 mmol/L– Sodium 139-142 mmol/L– Potassium 4.6 mmol/L– Creatinie 96 umol/L

Further investigations

Plasma osmolality – 300mosm/kg TSH 2.4mU/L FT4 8.3pmol/L, FT£ 3.0pmol/L PRL 1044mU/L C Ca 2.66 mmol/L, PTH 5.9 mmol/L Cortisol 564 nmol/L LH 0.5iU/L, FSH 3.0 iU/L

Ophthalmology review

Bitemporal hemianopia

Pituitary MRI

Suprasellar cystic mass I2  1  x  2.5  x  3  .2  cm.  It  ispredominantly  cystic  although  there  are  two  enhancingnodules  within  it. 

The  mass  displaced  adjacent  structures,most  notably  the  optic  chiasm  which  is  stretched  andcompressed. 

Mass extended into pituitary fossa but did not arise from the piuitary

Likely craniopharyngeoma

Management

Commenced on– Hydrocortisone 10mg/5mg/5mg– Levothyroxine 50mcg– Desmopressin acetate orally 100mcg bd

Urgent referral to neurosurgeons

Progress

Underwent pituitary surgery Histology confirmed a chordoma Awaiting proton beam radiotherapy

Plasma osmolality now 280-285 mosmol/L

Differential diagnosis of polydipsia/polyuria

Diabetes mellitus Hypercalcaemia Diabetes insipidus

– Cranial– Nephrogenic (genetic X linked, litjium,

domeclocycline) Psychogenic polydipsia

Causes of cranial DI

idiopathic head injury and neurosurgery neoplastic - pituitary tumour, craniopharyngioma,

dysgerminoma, hypothalamic metastases - often in children

infectious - meningitis, encephalitis granulomatous disease - sarcoidosis, histiocytosis vascular - aneurysm, sickle cell anaemia,

Sheehan's syndrome drugs - ADH secretion is suppressed by naloxone,

ethanol and phenytoin

Investigations

Electrolytes Urea/creatinine Plasma osmolality/urine osmolality Glucose Calcium 24 hour urine collection Pituitary screen (TSH, FT4, PRL, cortisol, LH/FSH,

ILGF1) Visual field tests Pituitary MRI

Water deprivation test

Baseline– Weight– Plasma and urine osmolality– Serum electrolytes

Deprive of water, and food Under constant supervision Monitor hourly serum/urine osmolality, urine output and weight Primary polydipsia - If urine concentrates and serum osmolality

remains low If plasma osmolality >300 mosmol/L or 5% wt loss then give

DDAVP and allow to drink Recheck serum and urine and expect to see 1:2 ratio (serum to

urine osm) in cranial DI, patinents with nephrogenic DI will not concentrate their urine

Treatment

Desmopressin

– Inranasally- 10-40mcg daily divided doses– By mouth 0.2-1.2mg daily divided doses

Titrate dose to symptoms Monitor electrolytes and osmolality

Conclusions

Adequate investigation required Presentation can often be subtle/missed Initial urine/plasma osmolality may be

falsely reassuring Can be first presentation of severe

intracranial pathology