Endocrine - SIADH/DI, DKA/HHS, hypoglycemia, Adrenal Insufficiency, Thyroid Emergencies

Serum Osmolality - what is it? what causes an increase?

• the measure of the number of particles in a solution (serum)

  • endocrine problems often result in serum osmolality problems

  • expressed in milliosmoles; normal = 275-295 mOsm/kg

  • cell membranes are permeable to water → therefore serum osmolality will affect the intracellular fluid (ICF) osmolality

• INCREASES IN serum sodium, BUN, and/or glucose will INCREASE SERUM OSMOLALITY

Hypothalamus - what is it? what does it regulate? what glands does it NOT control?

• hypothalamus (via the pituitary gland) is the endocrine “monitoring center”

• REGULATES: temperature, intake drives, and autonomic nervous system (sympathetic/parasympathetic)

• ONLY THE PANCREAS AND THE PARATHYROID GLAND release hormones that are not controlled by the hypothalamus

Antidiuretic Hormone (ADH) - what is it?

• a hormone formed in the hypothalamus and is stored in the posterior pituitary gland

• works on the distal convoluted tubules and the collecting tubules of the kidneys to reabsorb water (which prevents diuresis) → THEREFORE DETERMINING URINE CONCENTRATION

  • normal urine specific gravity is 1.010-1.020 (less than 1.010 is DILUTED urine; more than 1.020 is CONCENTRATED urine)

Syndrome of Inappropriate ADH (SIADH) - PATHOPHYSIOLOGY

• INCREASE in ADH production

• → kidneys retain water

• →LOW URINE OUTPUT

• →dilutional hyponatremia (DECREASED serum sodium) and DECREASED serum osmolality

Syndrome of Inappropriate ADH (SIADH) - etiology

• neurogenic (such as stroke, pituitary tumor)

• pulmonary (such as viral pneumonia, oat cell CA, TB, positive pressure ventilation)

• pharmacological agents (such as thiazide diuretics, haloperidol, amiodarone)

  • WHAT IS THE BIGGEST DANGER OF HYPONATREMIA? → SEIZURES

Syndrome of Inappropriate ADH (SIADH) - Treatment

• address etiology

• medication adjustment (as indicated)

• fluid restriction

• 3% saline (generally reserved for a serum sodium less than 120 mEq/L)

• administer phenytoin (Dilantin) → INHIBITS ADH secretion

• NO hypotonic solutions or free water

• monitor for complications (seizures, increased ICP, coma)

Diabetes Insipidus (DI) - PATHOPHYSIOLOGY

• DECREASE in ADH production

• →kidneys lose water→ HIGH URINE OUTPUT

• →HYPERNATREMIA due to water loss (increased serum sodium)

• AND increased serum osmolality

• AND urine output of 6-24 L/day + LOW urine specific gravity (DILUTED)

Diabetes Insipidus (DI) - etiologies? complication?

• neurogenic (trauma, tumor, craniotomy)

• drugs (phenytoin, ethanol)

• nephrogenic (renal transplant, polycystic kidneys)

• COMPLICATION - HYPOVOLEMIA/HYPOVOLEMIC SHOCK

Diabetes Insipidus (DI) - TREATMENT

• identify etiology and address

• administer fluids (amount and type depending on BP, electrolytes, serum osmolality)

• monitor urinary output/specific gravity

• give ADH (Pitressin (Vasopressin), DDAVP (Desmopressin)). use cautiously for those with heart disease, since ADH may cause coronary artery ischemia

DKA vs. HHS - etiologies

• DKA:

  • YOUNGER age; history/new onset of Type 1 diabetes; infection; stress; noncompliance

• HHS:

  • OLDER age; Type 2 diabetes; Pancreatitis; TPN; Medications (steroids, thiazide diuretics, phenytoin, atypical antipsychotics)

DKA vs. HHS - blood sugar? fluid loss? insulin production?

• DKA:

  • blood sugar - GREATER than 250

  • fluid loss - 4-6 L

  • insulin production - NONE

• HHS:

  • blood sugar - GREATER than 600

  • fluid loss - 6-9 L

  • insulin production - yes, but NOT ADEQUATE

DKA vs. HHS - development? acidosis present? ketones (positive/negative)?

• DKA:

  • Develops - RAPIDLY over 1-2 days (NO INSULIN PRODUCTION)

  • acidosis present? - YES

  • ketones? - POSITIVE (HIGH LEVELS)

• HHS:

  • Develops - SLOWLY over 5-7 days (still making SOME insulin)

  • acidosis present? - no (UNLESS HYPOVOLEMIC SHOCK IS PRESENT)

  • ketones? - negative OR positive, with LOW LEVELS

DKA vs. HHS - serum osmolality? breathing pattern?

• DKA:

  • serum osmolality - normal or high

  • breathing pattern - KUSSMAUL (DEEP, rapid, labored breathing → trying to blow off CO2)

• HHS:

  • serum osmolality - GREATER than 320 mOsm/kg

  • breathing pattern - SHALLOW, RAPID

DKA vs. HHS - TREATMENT

• DKA:

  • insulin, fluids

  • 0.9 NS, or, if the sodium is high and the BP is normal/high, use 0.45 saline

  • decrease blood sugar by 50-100 PER HOUR

  • add dextrose to the IV fluids after the serum glucose reaches ~250 (MAKE SURE IT DOES NOT DROP TOO LOW!!)

  • continue insulin infusion until the acidosis has resolved

• HHS:

  • fluids (0.9 NS), insulin

  • decrease blood sugar by 50-100 PER HOUR

  • add dextrose to IV fluids after serum glucose reaches ~300

DKA vs. HHS - SERUM POTASSIUM

• DKA:

  • INCREASED potassium in the presence of acidosis, although the total body potassium is low; serum potassium DECREASES as the acidosis is corrected

• HHS:

  • often INCREASED due to insulin deficiency

DKA/HHS - METABOLIC ACIDOSIS

• during metabolic acidosis, H+ ions moves INTO the INTRACELLULAR space

  • → IN EXCHANGE, potassium LEAVES intracellular space, resulting in HYPERKALEMIA (yet the total body potassium has not increased)

• in the presence of metabolic acidosis, for every 0.1 decrease in pH, the serum potassium INCREASES by 0.6 mEq/L

  • ex:

    • pH of 7.2, expected potassium would be 5.2 (if K is normal, there is a state of relative hypokalemia)

    • pH of 7.0, expected potassium would be 6.4 (if K is normal, there is a state of EXTREME relative hypokalemia)

      • BE CAREFUL!! → as you fix the acidosis, the potassium will continue to drop!!

• DKA? - there may be a total body hypokalemia due to diuresis, which occurred as A RESULT OF ELEVATED BLOOD SUGAR

Acute Hypoglycemia - etiologies

• insulin (dose was more than what was necessary for body requirements)

• oral hypoglycemia agents (if dose was more than necessary/dose was NOT adjusted as renal insufficiency developed)

• increase in physical activity for diabetics, which may INCREASE the utilization of glucose

• sepsis (NOT WELL UNDERSTOOD)

• **BETA BLOCKERS mask the early signs of hypoglycemia (for Type 1 diabetes)

  • → the first symptoms they will experience ARE THE LATE ONES!!

Acute Hypoglycemia - INITIAL symptoms/LATE symptoms

• INITIAL SYMPTOMS (due to sympathetic effects of adrenaline release in an attempt to raise the level of glucose)

  • shakiness; palpitations; sweating; moodiness; inability to concentrate

• LATE SYMPTOMS (due to a lack of glucose in the brain)

  • confusion, abnormal behavior; difficult to arouse; slurred speech; seizure; loss of consciousness

Acute Hypoglycemia - TREATMENT

• complex carbs by mouth if the patient is able to swallow

• 50% dextrose if the patient is unable to take oral carbs (IV 50% dextrose may IRRITATE THE VEIN!!!)

• 10% dextrose infusion for refractory hypoglycemia

• Glucagon 1mg IM

  • NOTE: it decreases GI motility

  • monitor for N/V; position the patient on his or her side in order to prevent aspiration

Acute Adrenal Insufficiency/Crisis - OVERVIEW

• adrenal glands produce CORTISOL (both glucocorticoids and mineralocorticoids); adrenal crisis may develop due to acute insufficiency of these adrenal hormones

• LIFE THREATENING!

• chronic adrenal insufficiency may be seen in the presence of Addison’s disease

Acute Adrenal Insufficiency/Crisis - etiologies? clinical presentation?

• etiologies - sepsis, trauma, head injury, medications (ketoconazole, phenytoin, rifampin, mitotane, ABRUPT WITHDRAWAL OF CORTICOSTEROIDS), acute physical stress, and/or inadequate medical treatment for someone with known Addison’s disease

• clinical presentation - AMS, weakness, severe hypotension, N/V, fever, and/or abdominal pain

Acute Adrenal Insufficiency/Crisis - LAB FINDINGS? what scans should patients get?

• LAB FINDINGS - hypoglycemia, hyponatremia, hyperkalemia, hypercalcemia, and/or low blood ACTH and cortisol (drawn PRIOR to treatment with steroids)

• suspected patients will need:

  • CT scan of abdomen - to rule out adrenal hemorrhage or calcification of the adrenal glands

  • CT of head - to assess pituitary gland

Acute Adrenal Insufficiency/Crisis - TREATMENT FOR CRISIS

• RAPID IDENTIFICATION!!

  • fluids/glucocorticoid replacement

    • normal saline or 5% dextrose in normal saline (if patient is hypoglycemic), using the volume status and UOP to guide resuscitation

  • steroids

    • if the patient does NOT have a history of adrenal insufficiency, give dexamethasone (4 mg IV bolus); do NOT use hydrocortisone until testing (to rule out underlying adrenal insufficiency) is completed

      • the patient will also need an ACTH stimulation test after he or she is stabilized

    • if the patient has known adrenal insufficiency, give hydrocortisone (100 mg IV bolus)

    • administer vasopressors if the patient’s blood pressure is not responsive to fluids

Thyroid Crisis (storm) - what is it? etiologies?

• occurs in patients with known HYPERTHRYOID disease, in which there is increased action of T3 and T4 hormones, resulting in a life-threatening emergency

  • etiologies? - infection, DKA, complications during labor/delivery, seizure disorder, radioactive iodine treatment/iodinated contrast dyes, multinodular goiter, poor compliance with antithyroid therapy and/or thyroxine overdose

  • medications that may precipitate a thyroid storm include amiodarone, an ASA overdose, cytotoxic chemotherapy, insulin, lithium, thiazide diuretics, and/or tricyclic antidepressants

Myxedema Coma (SEVERE HYPOTHYROIDISM) - what is it? etiologies?

• occurs in patients with known hypothyroid disease, and results from a severe DEFICIENCY of thyroid hormones, creating a life-threatening emergency

  • etiologies? - sepsis, stroke, heart failure, trauma or other physical stress, and/or a discontinuation of or inadequate dose of thyroid medication

Thyroid Storm - signs/symptoms

• Altered mental status (confusion, psychosis, paranoia, coma)

• hyperkinesis, tremor, agitation

• FEVER; warm, moist, flushed skin

• TACHYcardia

• TACHYpnea

• enlarged neck, goiter

• lab abnormalities

  • INCREASED total T3, T4, and INCREASED free T3, T4

  • DECREASED TSH (high levels of T3/T4 suppresses TSH secretion)

  • INCREASED LDH (d/t extreme hypermetabolic state/cellular stress), INCREASED Bilirubin

Myxedema Coma - signs/symptoms

• Altered level of consciousness, disorientation, poor memory, depression, coma

• delayed DTRs

• HYPOthermia

• BRADYcardia

• SLOW/SHALLOW respirations

• macroglossia, vocal cord edema

• Lab abnormalities:

  • INCREASED TSH; DECREASED T3 and T4

  • INCREASED LDH, INCREASED CK

  • anemia

  • respiratory acidosis, hypoxemia

Thyroid Storm - TREATMENT

• begin cooling, prevent shivering

• IV fluids/electrolytes

• plasmapheresis, therapeutic plasma exchange

• medications

  • propylthiouracil (stops thyroid hormone synthesis)

  • iodine or lithium (blocks thyroid hormone release)

  • propranolol (reduces T4→T3 conversion; decreases HR/contractility/myocardial oxygen demand)

  • acetaminophen for a fever (do not administer ASA, which inhibits the binding of T3 and T4, thereby increasing T3 and T4)

  • glucocorticoids

Myxedema Coma - TREATMENT

• begin rewarming

• support the airway and provide ventilation as needed

• prevent infections

• administer (SLOWLY) 3% saline for severe hyponatremia

• medications

  • levothyroxine (Synthroid) IV

  • glucocorticoids if patient is hypotensive despite adequate fluid resuscitation

• rule out adrenal crisis (which may mimic hypothyroidism)