Medical grandrounds on diabetes insipidus
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MEDICAL GRANDROUNDS ON DIABETES INSIPIDUS. Desiree B. Yano-Simbulan, M.D. Maricel B. Peniero, M.D. November 8, 2007. LEARNING OBJECTIVES. To present a case of a 50 year old female with diabetes insipidus To provide an overview in the diagnostic approach to polyuria and diabetes insipidus

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MEDICAL GRANDROUNDS ON DIABETES INSIPIDUS

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Medical grandrounds on diabetes insipidus

MEDICAL GRANDROUNDSONDIABETES INSIPIDUS

Desiree B. Yano-Simbulan, M.D.

Maricel B. Peniero, M.D.

November 8, 2007


Learning objectives

LEARNING OBJECTIVES

  • To present a case of a 50 year old female with diabetes insipidus

  • To provide an overview in the diagnostic approach to polyuria and diabetes insipidus

  • To discuss nephrogenic versus central diabetes insipidus: etiology, clinical manifestation, work up and management


Identifying data

IDENTIFYING DATA

  • A.G.

  • 50y/o female

  • Filipino

  • cc: epigastric pain


History of present illness

HISTORY OF PRESENT ILLNESS

2 weeks PTA(+)epigastric pain

(+)bloatedness

(+)loss of appetite (-) nausea, vomiting

(-)changes in bowel habit

EGD: Gastritis

Gastric polyp

Few days PTA(+)persistence of symptoms

A


Review of systems

REVIEW OF SYSTEMS

  • No fever

  • No blurring of vision, no visual loss

  • No throat pain, tinnitus, no hearing loss

  • No dyspnea, no cough, no hemoptysis

  • No chest pain, no palpitation, no orthopnea

  • (+) polydipsia (+) polyphagia (+) nocturia

  • (+) right hip pain (+) low back pain

  • No skin rash or skin changes


Past medical history

PAST MEDICAL HISTORY

  • Invasive Ductal Carcinoma, Left Breast

    s/p Modified Radical Mastectomy,left breast 2003

    s/p Chemotherapy 2003, 2004

    s/p Radiotherapy, 2006

  • Hypertension, 2004

    Atenolol (Therabloc) 50mg 1/2tab OD

    Imidapril (Vascor) 5mg OD

  • Diabetes Mellitus, 2000

    Acarbose (Glucobay) 50mg OD

    Repaglinide (Novonorm) 0.5mg OD

  • s/p laparoscopic cholecystectomy, 2004


Family history

FAMILY HISTORY

  • (+) Breast cancer – 2 cousins

  • (+) Diabetes Mellitus – mother, brother


Personal social history

PERSONAL/SOCIAL HISTORY

  • non smoker

  • non alcoholic beverage drinker

  • no history of substance abuse

  • worked as a general accountant


Physical examination

PHYSICAL EXAMINATION

Gen. Survey: Awake, alert not in cardiorespiratory distress

Vital Statistics: Ht:157cmWt:58kgs BMI: 23

Vital Signs: BP:110/70 CR:95 RR:20 To:36.6

Skin: warm, moist, no rash

HEENT: pink palpebral conjunctivae, anicteric sclerae,

supple neck, no tonsillopharyngeal congestion, no neck vein distention, JVP = 10cm


Physical examination1

PHYSICAL EXAMINATION

Chest: symmetrical chest expansion, (-) intercostal retraction (-) rales (-) wheezes (+) 10cm well healed incisional scar left chest

Cardiac: Adynamic Precordium, regular S1S2, apex beat at 5th LICS MCL, (-) murmur (-) thrill

Abdomen: Globular, NABS, (-) bruits, normo-tympanic, (+)epigastric tenderness (-) organomegaly

Extremities: (-)edema (-) cyanosis, full and equal pulses


Admitting diagnosis

ADMITTING DIAGNOSIS

  • Gastritis, Gastric polyp s/p EGD

  • Hypertensive Cardiovascular Disease II

  • Diabetes Mellitus Type II

  • Invasive Ductal Carcinoma, Left Breast, 2003

    s/p MRM, left breast

    s/p chemotherapy

    s/p radiotherapy


Course in the wards

COURSE IN THE WARDS


1 st hospital day

1st HOSPITAL DAY

  • Diagnostics

    • CBC

    • Spec 16

    • CT of chest and abdomen

  • Endocrine Referral for blood sugar

    control

    • CBG monitoring(initial CBG= 243mgs%)

    • FBS (207mgs%), HbA1c (9.6%)

    • Acarbose (Glucobay) 50mg TID

    • Glimepiride (Solosa) 2mg OD


Medical grandrounds on diabetes insipidus

CBC


Urinalysis

Urinalysis

Coloryellow

Transparencyclear

pHacidic

Specific Gravity1.020 (1.015-1.025)

Sugar(-)

Protein (-)

Ketones (-)

Nitrites (-)

Leucocyte Esterases+1

Blood (-)

RBC0.1

WBC2.5

Epithelial cells0.2

Bacteria82

Mucus Threads(-)

Crystals(-)

Cast(-)


Spec 16 done as opd

SPEC 16 (done as OPD)

Corrected Na 136

(CBG-100) x0.016 +Na

Corrected Ca 12.6

(4-albumin) x0.8 +Ca


Medical grandrounds on diabetes insipidus

  • K = 2.9

    • KCL incorporation (30meqsKCL +PNSS1L x10h)

       Repeat K 5.0 (n.v. 3.5-5.1)

  • Ca = 12.6

    • ionized Ca(1.66mmol/L) (n.v. 1.12-1.32)

    • phosphorus(3.7mgs%) (n.v. 2.3-4.7)

    • intact PTH (1.637pg/ml)(n.v. 10-65)


3 rd hospital day

3rd Hospital Day

NEPHROLOGY referral for electrolyte management

  • Ca = 12.0 ( 12.1)

    • Hydration with PNSS at 200cc/h x 4hours, then back to 120cc/h

    • Diuresis with Lasix 20mg IV q8

    • Serial electrolyte monitoring

    • Accurate I/O monitoring


4th hospital day

4th Hospital Day

  • Ca = 12.2 12.0 after Lasix and PNSS

    • Impression

      Hypercalcemia of Malignancy

    • Plan

      Ibandronic Acid (6mg in PNSS500cc x1hr)

      Lasix discontinued

      Continue hydration, PNSS 1Lx120cc/h


Ct scan of chest and abdomen

CT Scan of Chest and Abdomen

  • Multiple osseous lytic lesions in the thoracolumbar spine, likely metastatic

  • Minimal bilateral pleural effusion with parenchymal consolidation in the right lower lobe, atelectasis vs pneumonia

  • No interval change in size of subcm nodule in lingula

  • Mediastinal, right hilar and right axillary lymphadenopathy showing significant increase in size since september 27, 2006

  • Heterogeneous enhancement with slight nodularity of the right breast tissue.

  • Post mastectomy, left


4 th hospital day

4th Hospital Day

  • Medical Oncology Referral

    • Impression

      Breast Ca IV, bone and lung metastases

      with inflammatory breast changes, right breast

    • Plan

      For repeat chemotherapy


4 th hospital day1

4th Hospital Day

  • Pain Management Referral

    for right hip pain, low back pain

    • Paracetamol/Tramadol (Dolcet) 1 tab TID

    • Gabapentin 100mg BID

    • Fentanyl 25mcg IV  Fentanyl PCA


5 th hospital day

5th Hospital Day

  • uncontrolled Hyperglycemia

    (CBG =406mgs%)

    • OHA discontinued

    • Insulin drip

    • Hourly CBG monitoring

    • K monitoring ( K = 3.3)

    • KCL incorporation


6 th hospital day bone scan

6th Hospital Day – Bone Scan

Foci of increased radioactivity situated in several areas of the body, namely: frontal, parietal, and occipital regions of the skull, both shoulder regions, both scapulae, both humerii, sternum, all levels of the thoracic and lumbosacral spine, both sides of the pelvis, both femora, both tibia, and multiple rib segments bilaterally. Above findings are not demonstrated in the previous study done in October 2006

Impression: Findings are compatible with

Osseous Metastases


Medical grandrounds on diabetes insipidus

  • Zoledronic acid (Zometa) 4mg in D5W100cc x20min

  • Allopurinol 300mg OD


8 th hospital day mri of the cervical and thoracic spine

8th HOSPITAL DAY – MRI of the Cervical and Thoracic Spine

Extensive bone metastases involving the cervical and thoracic spine with compression deformities of T2 and T6 vertebral bodies. No evidence of spinal canal metastasis

Extensive mediastinal lymphadenopathy


Medical grandrounds on diabetes insipidus

  • Dexamethasone 5mg IV q 6hr RTC

  • Nexium 40mg IV OD


10 th hospital day

10th Hospital Day

  • Radiation Oncology Referral

    for spinal cord compression

    • For radiation therapy

    • 900 cGy to upper thoracic spines,

      10 sessions over 2 weeks


12 th hospital day

12th Hospital Day

  • Polyuria (Urine output 8.8/L)

    • Na (155)

    • Urine Osmolality (120 mosm/kg) (n.v.301-1093)

    • Plasma Osmolality (326 mosm/kg) (n.v.275-295)

    • Increase oral fluid intake

    • Increased hydration with D5W 1L x100cc/h  150cc/h, later shifted to 0.3% NSS 1L x 150cc/h


Urinalysis1

Urinalysis

Coloryellow

Transparencyhazy

pHneutral

Specific Gravity1.010(1.015-1.025)

Sugar+2

Proteintrace

Ketones (-)

Nitrites (-)

Leucocyte Esterases+1

Blood (-)

RBC0.2

WBC6.6

Epithelial cells1.3

Bacteria291

Mucus Threads(-)

Crystals(-)

Cast(-)


Osmolar clearance vs free water clearance

Osmolar Clearance vs Free Water Clearance

Solute

H20

urine

Uosm x V

--------------

Posm

Osmolar

Clearance (Cosm) =


Medical grandrounds on diabetes insipidus

Uosm = 120

Posm = 326

Vol = 8.8L

Cosm = 120 x 8.8

326

Cosm = 3.23L

3.3L (Osm)

Urine vol =8.8L

5.5L (H20)


Medical grandrounds on diabetes insipidus

Conclusion

  • Polyuria is secondary to water diuresis


Medical grandrounds on diabetes insipidus

  • Polyuria secondary to water diuresis

    • Nephrogenic DI (? hypercalcemia)

    • vs Central DI (? metastasis)

  • Trial of DESMOPRESSIN (0.2mcg 1/2tab BID)

    • Effect on urine volume and osmolality


After the trial of desmopressin

After the trial of Desmopressin

  • Urine Volume 100%

    8.8L  4.6L

  • Urine Osmolality 100%

    120  423

WITHDRAWAL OF DESMOPRESSIN

Urine OSMOLALITY: 423  213

Conclusion : CENTRAL Diabetes Insipidus


Medical grandrounds on diabetes insipidus

Urine Osmolality

Urine Volume


Input and output monitoring

Input and Output Monitoring


16 th hospital day brain mri

16th HOSPITAL DAY – Brain MRI

Nodules in the pineal region and hypothalamus withthickening of the pituitary stalk. Enhancing nodules in the left parieto occipital area, head of the right caudate nucleus, left basal ganglia, left cerebellar hemisphere. Leptomeningeal thickening and enhancement, left temporal area. Enhancing bone foci in both frontoparietal and left temporal bones.

Above findings considered metastases


Clinical outcome

Clinical Outcome

  • Discharged stable on the 24th hospital day


Polyuria and diabetes insipidus

POLYURIA AND DIABETES INSIPIDUS


Polyuria

POLYURIA

  • Polyuria can be arbitrarily defined as a urine output exceeding 3 L/day in adults and 2 L/m2 in children

  • Causes

    • Primary polydipsia

    • Central Diabetes Insipidus

    • Nephrogenic Diabetes Insipidus


Diagnostic approach to polyuria

Diagnostic Approach to Polyuria

  • Onset of polyuria

  • Family history

  • Plasma Na concentration

    • Na <137 meq/L, due to water overload, is usually indicative of primary polydipsia

    • Na >142 meq/L, due to water loss, points toward DI

  • Water restriction test

  • Plasma ADH measurement


Water restriction test

Water Restriction Test


Solute diuresis

Solute Diuresis

  • Glucosuria

  • High-protein feedings

  • Volume expansion due to saline loading

  • Differentiated from diabetes insipidus

    • Water diuresis

      Uosm <250

    • Solute diuresis

      Uosm >300 mosmol/kg

    • Total solute excretion markedly increased


Central diabetes insipidus

Central Diabetes Insipidus

  • Decreased release of ADH

  • Lack of ADH can be caused by disorders that act at one or more of the sites involved in ADH secretion:

    • hypothalamic osmoreceptors

    • supraoptic or paraventricular nuclei

    • superior portion of the supraopticohypophyseal tract


Etiology of central diabetes insipidus

Etiology of central diabetes insipidus

  • Idiopathic

  • Neurosurgery

    a. Craniopharyngioma

    b. Transphenoidal surgery

  • Head trauma

  • Hypoxic or ischemic encephalopathy

    a. Cardiopulmonary arrest

    b. Shock

    c. Sheehan syndrome

  • Neoplastic

    a. Primary : craniopharyngioma, cyst, pinealoma

    b. Metastatic : breast, lung

  • Miscellaneous


Review of literature

Review of Literature

SYSTEMIC CANCER PRESENTING AS DIABETES INSIPIDUS -

Clinical and radiographic features of 11 patients with a review of

metastatic-induced diabetes insipidus

“…of 100 consecutive cases of DI of any cause, diabetes insipidus

was the initial presentation in 11 patients with systemic

cancer. In these 11 patients, the most common sources metastatic to the

posterior pituitary-hypothalamic region were lung, breast,

leukemia and lymphoma. CT scanning demonstrated pituitary stalk

enlargement, suprasellar masses, or both…”

Kimmel D.W., O'Neill B.P., Systemic cancer presenting as

diabetes insipidus. Clinical and radiographic features of 11

patients with a review of metastatic-induced diabetes

insipidus. Cancer 1983 Dec 15;52(12):2355-8.


Review of literature1

Review of Literature

PITUITARY METASTASIS IN BREAST CARCINOMA

“…the incidence of metastasis to pituitary in breast cancer is reported as0.95%. Breast cancer and lung cancer are the most common primary sites, in women and men respectively, which metastasize to the pituitary. The presenting symptoms include diabetes insipidus, anterior pituitary insufficiency and retro-orbital pain. Metastases to the posterior lobe are more common than to the anterior lobe...”

Rao SR, Rao RS, Pituitary metastases in carcinoma breast. Shushrusha Hospital, Mumbai, India. JPGM

2001 Volume 47 Issue2 Page 135-6


Drug therapy of central diabetes insipidus

Drug therapy of central diabetes insipidus

  • ADH preparations

    a. Desmopressin nasal spray

    b. Aqueous vasopressin

    c. Lysine vasopressin nasal spray

    d. Vasopressin tannate in oil

  • Drugs that potentiate ADH effect

    a. Chlorpropamide

    b. Carbamazepine

    c. NSAIDS

  • Drugs that increase ADH secretion

    a. Clofibrate

  • Drugs not requiring ADH

    b. Thiazide diuretics


Nephrogenic diabetes insipidus

Nephrogenic Diabetes Insipidus

  • Decrease in urinary concentrating ability that results from ADH resistance

  • Resistance at the ADH site of action in the collecting tubules, or interference with the countercurrent mechanism due to medullary injury or to decreased sodium chloride reabsorption in the medullary aspect of the thick ascending limb of the loop of Henle


Etiology of nephrogenic diabetes insipidus

Etiology of nephrogenic diabetes insipidus

  • Congenital ( mutations in AVPR2 gene and aquaporin-2 gene

  • Hypercalcemia

  • Hypokalemia

  • Drugs

    a. Lithium

    b. Demeclocycline

    c. Streptozotocin

  • Pregnancy

  • Acute and chronic renal failure


Drug therapy of nephrogenic diabetes insipidus

Drug therapy of nephrogenic diabetes insipidus

  • Low sodium, low protein diet

  • Thiazide diuretic

  • Amiloride, K sparing diuretic

  • NSAIDS

***


Thank you

Thank you!


Xeloda capecitabine 150mg 500mg

Xeloda (Capecitabine) 150mg, 500mg

  • Antimetabolite

  • Pyrimidine analog

  • Inhibits DNA, RNA synthesis

  • Renal dose adjustment

  • CrCl 30-50 : decr start dose 25%

  • CrCl <30 : contraindicated


Serial electrolyte monitoring

Serial Electrolyte Monitoring


Serial electrolyte monitoring1

Serial Electrolyte Monitoring


Medical grandrounds on diabetes insipidus

Clinicopathologic review of 88 cases of carcinoma metastatic to the putuitary gland.

Teears RJ, Silverman EM

Cancer. 1975 Jul;36(1):216-20

Clinical and pathologic features of 88 cases of carcinoma metastatic to the pituitary gland were reviewed.In 61 (69.3%), metastases were localized either in the posterior lobe alone or in the posterior and anterior lobes together; only 12 (13.6%) involved the anterior lobe alone. Diabetes insipidus was present in 6 patients (6.8%), one of whom also had clinical panhypopituitarism due to metastatic tumor and necrosis in the anterior pituitary lobe. Breast and lung were the most frequent primary sites in women and men, respectively. Sixty-four (72.7%) of these glands were grossly normal at necropsy. Metastases to the pituitary gland occur more frequently in the posterior lobe than in the anterior lobe, and my ve reflected clinically by diabetes insipidus in patients with diseminated carcinoma. Clinical panhypopituitarism is a rare accompaniment of anterior lobe involvement


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