Diabetes Insipidus

Production of arginine vasopressin – by magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus.  Transported to the neurohypophysis via hypothalamo-hypophyseal tract.  Injury to these structures leads to DI.

 

 

Triphasic response in DI:

1. First phase – DI caused by “stunning” of the magnocellular neurons, no AVP secretion.
2. Second phase – injured hypothalamic cells degenerate and release their stored AVP
3. Third phase – if majority of these neurons are destroyed, permanent phase of DI begins

 

 

 

Reference:

Schreckinger, Matthew, Nicholas Szerlip, and Sandeep Mittal. “Diabetes Insipidus Following Resection Of Pituitary Tumors”. Clinical Neurology and Neurosurgery 115.2 (2013): 121-126.

 

 

RANDOM NOTES ON Diabetes insipidus (DI)

Nephrogenic DI – renal insensitivity to vasopressin, acquired or genetic; lithium

Central DI – deficiency in production of ADH

• Related to extent of excision
• Usually transient phenomenon after surgery
• SIADH in second phase – follow serum Na on day 7
• Symptoms: polyuria, nocturia, polydipsia / thirst

 

Patients with DI, especially if drowsy and unable to maintain adequate fluid intake, can rapidly become dehydrated.

 

ALGORITHM:

Measure Is and Os hourly, sum every 6 hours

Foley catheter

Onset of dilute polyuria UOP >250cc/hr x2  hours

Check other reasons:

1. diuretics
2. large resuscitation
3. mannitol
4. hyperglycemic
5. salt wasting

Labs

1. USG <1.005
2. UOsm 50-200 (<serum)
3. Hypernatremia

? rountine serum Na – every 6 hours on day 1, then every 12h until stable, then daily x 1 week

Replace fluids

1. normal saline to replace previous hour output, switch to 0.45% saline if UO 4-6ml/kg/h, switch to D5W if >6 ml/kg/h
2. if awake, fluids ad libidum; may be able to maintain fluid balance by drinking to satiety, still DDAVP so patients can sleep comfortably at night

DDAVP (1-desamino-8-D-argnine vasopressin)

• DDAVP: activates V2R – water reabsorption in kidney; mobilizes water channel aquaporin to luminal membrane of DCT and CD
• Liquid form – given intranasal; oral tablet form; parenteral form

 

	Tablets	Spray	Solution for injection
Dose comparison	100 mcg	2.5 mcg	N/A
	200 mcg	5 mcg	Less than 0.5 mcg
	400 mcg	10 mcg	Less than 1 mcg

 

• Usual dose 1 ug q12h
• Empiric – give minimum dose required to control polyuria; goal to control nocturia, partial control of polyuria during the day
• Water retention à hyponatremia is a potential risk; patient education, serum NaHS

 

ENDOCRINE

Post-op complications: hematomas, epistaxis, HCP, CSF leaks, meningitis

Preop labs with hypopituitarism – stress doses of hormonal replacement; keep on physiological dose until outpatient assessment

Lab tests post-op for evidence of early endocrinological remission

Cushing – no steroids unless necessary; serum cortisol q6h until nadir; if <5 + symptoms, start glucocorticoid therapy and then transition to maintenance doses until outpatient reassessment

Normal cortisol function prior to surgery – no steroids; assess post-o with AM fasting cortisol on POD1 or POD2; new start steroid replacement if cortisol <10 until reassessed outpatient

Acromegaly – POD1 serum GH level predicts early remission; delayed IGF1 level 6 weeks after

Prolactinomas – POD 1 AM prolactin level normalizes with remission

 

Classification and Severity of Diabetes Insipidus

Interesting classification of DI, taken from Neurology India, groups DI into mild and severe based on some clinical and lab findings.

 

 

This was their protocol for diagnosis and management of DI in patients who underwent craniopharyngioma surgery.

 

Protocol for diabetes insipidus

• Diagnosis:  UO > 4ml/kg/h over 6 h perior OR Na >145 mEq/L with USG <1.005
• Monitoring
  • if drowsy, unable to drink – measure Is and Os hourly, sum every 6 hours
  • Foley until UO reasonably controlled
  • intraop Na if surgery >6h determines type of IV fluids and if pitressin required in OR
  • measure Na q6h day 1
  • measure Na q12h day 2 until stable x 3 days
  • measure Na daily x 1 week
• Treatment
  • Fluids until patient is awake and demonstrates intact thirst mechanism
    • 0.45% saline when UO 4-6 ml/Kg/h
    • D5W when UO >6ml/kg/h
  • DDAVP
    • day 1 – 5 unit IV boluses of pitressin
    • started as early as possible, usually on 2nd day, oral DDAVP 100 ug tablets of fractions of tablets
• Adequacy of control
  • based on serum Na rather than Is and Os
    • check frequency >150 or <130 or inc/dec by >10mEg/L in 1 day

 

Other pearls:

• Adipsia may be complication of hypothalamic damage
  • diminished thirst sensation
  • higher risk of developing hpyernatremia
  • require round the clock DDAVP
  • need to be trained to drink 2-3L water per day
  • gradually resolves with partial or complete thirst recovery by 9 months
• Polydipsic with high UO
  • patient compensating with increased PO intake, normal or low Na
  • at risk for water intoxication or hyponatremia
  • use oral rehydration solution rather than plain water

 

Reference:

Chacko, AriG et al. “Evaluation Of A Protocol-Based Treatment Strategy For Postoperative Diabetes Insipidus In Craniopharyngioma”. Neurology India 63.5 (2015): 712.

Euthyroid-Sick Syndrome

50% of patients in ICU may have low T3, T4 or TSH.  These patients were previously thought to be “euthyroid,” and were thought to have euthyroid-sick syndrome.  However, there is evidence that these patients may have acquired transient central thyroid dysfunction.

How to interpret TSH:

• low but detectable (0.05 to 0.3 mU/L) – will be euthyroid when reassessed after recovery
• undetectable (<0.01 mU/L) – 75% have hyperthyroidism
• high (up to 20 mU/L) – some hospitalized patients have transient elevations during recovery from nonthyroidal illness, few have hypothyroidismw hen re-evaluated after recovery
• very high (>20 mU/L) usually have permanent hypothyroidism

Graph below shows changes in thyroid function tests in nonthyroidal illness.

Thyroid function tests should not be measured on critically ill patients, unless thyroid dysfunction is suspected.  When thyroid dysfunction is suspected, TSH is inadequate and all methods of assessing free T4 are unreliable in severe critical illness.

Patients who are critically ill with low T3 and T4 and no other clinical signs of hypothyroidism should not be treated with thyroid hormone replacement.  Start thyroid replacement if there is evidence of hypothyroidism; in the absence of myxedema coma, start at half the expected full replacement dose.

TREATMENT:  No benefit with hormone replacement.

TAKE HOME:  Thyroid function should not be checked in critically ill patients unless you have a strong suspicion for thryoidal illness.

Reference:

“Thyroid Function In Nonthyroidal Illness”. Uptodate.com. N.p., 2016. 14 June 2016.

HBA1C

Notes:

1. RBCs have a life cycle of 8-12 weeks.
2. HbA1C is formed by glycation (attachment of glucose) to Hb and reflects glucose concentration of the previous 2-3 months.
3. HbA1C diagnostic of DM – 6.5% (48mmol/mol)
4. goal of DM management – <7%

Factors that alter the HbA1C value:

1. erythrocyte life span
   • increased lifespan – increases time RBC is exposed to glucose, increases HbA1C falsely, (ex. splenectomy)
   • decreased lifespan – HbA1C decreased (ex. hemolytic anemia)
2. erythropoiesis
   • decreased erythropoiesis – increases mean age of RBC, increases HbA1C level (ex. iron deficiency anemia)
   • severe CKD decreases erythropoietin levels
3. severe hypertriglyceridemia and chronic alcoholism
   • interferes with assay
4. Hb variants – yields inaccurate results
5. genetic factors or the “glycation gap”
   1. genes that affect RBC life span or glycation

ALTERNATIVE TESTING METHODS

 

1. glycated albumin and fructosamine (measures all glycated serum protein)
   1. half life of albumin is 14-21 days; all glycated serum protein tests reflect average blood glucose concentrations over the previous 2-3 weeks
   2. not affected by RBC disorders but by serum protein abnormalities (i.e. nephrotic syndrome)
2. daily fingerstick
3. continuous glucose monitor
4. serum 1,5 anhydroglucitol (1,5-AG) test

 

CONVERSION A1C EST AVE BLOOD GLUCOSE:

The formula for converting A1C to an estimated average blood glucose level, according to the American Diabetes Association, is (28.7 x A1C) – 46.7 = estimated average glucose.

Conversion table (A1C to EAG)

 

References

O’Keeffe, Derek T., Spyridoula Maraka, and Robert A. Rizza. “Hba 1C In The Evaluation Of Diabetes Mellitus”. JAMA 315.6 (2016): 605. Web. 13 Feb. 2016.

Nhrmc.org,. N.p., 2016. Web. 13 Feb. 2016.  https://www.nhrmc.org/~/media/files/ diabetes-health-plan/class-materials/diabetes-overview-class/conversion-table-revised-12-30-14.pdf?la=en

 

NSUH Protocol for Management of Inpatient Hyperglycemia

Initiation of Subcutaneous Insulin

Basal and Nutritional Insulin

Adjustment of Insulin Dose

Cosyntropin Test

Cholesterol Guidelines

ACC AHA Task Force on Practice Guidelines

Treatment of  High Blood Cholesterol

4 subgroups where benefit clearly outweighs risk of statin therapy:

1.  (+) atherosclerotic cardiovascular disease

2.  LDL >/=190mg/dL

3.  LDL >/=70mg/dL +  DM

4.  LDL >/=70mg/dL + >/=7.5% 10-year risk of atherosclerotic cardiovascular disease

**Lower LDL by >/=50%, use high-intensity statin therapy

Groups for which no evidence or statin not recommended:

1.  >/=75y/o unless with clinical cardiovascular disease

2.  on HD

3.  NYHA 2-4

Other Notes:

1. target levels no longer emphsized; do not measure LDL routinely

2.  avoid non-statin agents

3.  do not use surrogate markers (CRP, calcium scores)

4.  use risk-calculator

http://static.heart.org/ahamah/risk/Omnibus_Risk_Estimator.xls&nbsp;

Notes from the actual 85-page guidelines:

Parathyroid Hormone (PTH) and Calcium

Correlation between PTH and Ca++ levels

Oral Antihypoglycemic Agents

Pathophysiolo of Metabolic Bone Disease in CKD