Endocrine Emergencies in
Obstetrics
Darren Farley, MD
Clinical Assistant Professor
Division of Maternal-Fetal Medicine
Dept. of Obstetrics and Gynecology
University of Kansas School of Medicine – Wichita
• No financial interests to disclose.
OUTLINE
• Diabetic Ketoacidosis
• Thyrotoxicosis & Thyroid Storm
• Pheochromocytoma
• Primary Hyperparathyroidism
• Adrenal crisis
• OB ICU Critical Care Manual –
– Dr. Michael Foley -
• Pregnancy changes
• Diagnosis
• Management
Diabetic Ketoacidosis
Case
• 26 yo P2002, type 1 DM, with
nephropathy, LVH, and CHTN
• What is best treatment during
pregnancy?
• 1-Amlodipine
• 2-Labetalol
• 3- Lisinopril
• 4- 1,2
• 5-No treatment unless BP >180/110
DM classification• Type 1 – typically diagnosed before
pregnancy
– Low c-peptide can help differentiate
• Type 2 – cannot be diagnosed during
pregnancy due to overlap of potential early
onset gestational diabetes
– Even with early pregnancy elevated A1C
• Gestational diabetes – carbohydrate
intolerance of various degrees of severity,
with onset or first recognition during
pregnancy
White classification- modified
Class Description
A GDM – A1 –diet, A2 –insulin, oral rx
B (DM, type 1 or 2) Age of onset >20y, duration <10y
C Age of onset 10-20y, duration 10-20y
D Age of onset <10y, duration >20y,
benign retinopathy, HTN
R Proliferative retinopathy, vitreous
hemorrhage
F Nephropathy TP >500mg/d
RF See above
G Many pregnancy failures
H Arteriosclerotic heart disease
T Renal transplantation
Per UTD - Adapted from Hare JW, White JP. Diabetes Care 1980;3:394.
Glucose physiology in pregnancy
• Glucose production increases with
advancing gestational age
• Insulin resistance increases with
advancing gestational age
• Insulin response to glucose tolerance test
- increases with advancing gestational age
Incidence of DKA
• Nonpregnant -
– 1-5 episodes per 100 patients / year
– Mortality 5-10%
• Complicates 2-9% of diabetic pregnancies
• A leading cause of fetal loss
• Fetal mortality rate
– 1963 – 50-90%
– Now – 10-20%
• Maternal mortality - now 1% (previously 15-
50%)Foley p 143
DKA—signs/symptoms
Hyperventilation
Ketotic breath
Tachycardia
Hypotension
Dry MM
Disorientation
Coma
Polyuria
Polydipsia
N/V
Abdominal pain
Weakness
Weight loss
Factors precipitating DKA in
pregnancy
• Emesis
• Infection
• Non-compliance
• Insulin pump failure
• ß-sympathomimetic drugs
• Steroids
• Poor management
• PE
Diagnosis
• DKA -
• D –Diabetic - >180mg/dL
• K –serum acetone, Ketones 1:2 or greater
• A –Acidosis – arterial pH<7.3, HCO3-
<15, anion gap [Na – (Cl +HCO3)] >12
Management
• Maternal Resuscitation– IV fluids
– Insulin
– Search for underlying cause – infection, noncompliance, etc
– I/Os, monitoring glucose (q1-2hr),
– ABG, pH, anion gap, electrolytes (q2-4hr)
– Fetal monitoring*• Withhold intervention toward delivery on behalf of the
fetus until maternal metabolic disturbances are corrected
• Oxygen and correct maternal positioning while correcting disturbances
Management -
• Fluid replacement
– Fluid deficit is 100cc/kg (7-10L for total deficit)
• Accurate I/Os, BUN, Creatinine
• Replace 75% of deficit in 1st 24 hrs, remainder over the hospitalization
– NS (use isotonic solution to prevent rapid decline in plasma osmolarity and resultant cellular swelling and cerebral edema)
– 1L NS in first hour, 500 mL/hr hours 2 and 3 (NS 1st 3 hrs)
– LR or ½ NS at 250cc/hr in initial 24 hr until 75% of volume deficit is replaced
• LR is used to avoid further acidosis (LR pH 6.5, vs 5.0 of NS)
• Sodium load with NS – possible hypernatremia, switch to LR or ½ NS if Na >150meq/L
Insulin (0.1)
• Insulin therapy (inhibits lipolysis and ketogenesis, leads to suppression of hepatic glucose production)
– Loading dose 0.1U/kg regular insulin
• 50 units / 500 mL NS (1cc = 0.1units, 10 cc = 1unit)
– Infusion 0.1units/kg/hour
– If plasma glucose does not decrease by 10% in first hour or by 20% in second hour – repeat loading dose or double infusion rate
– When glucose ~250mg/dL or less, add D5 to the fluids and reduce the hourly rate by 1/2
– Continue infusion of insulin until serum bicarbonate and anion gap normalize
Insulin• Use regular insulin
• Pump monitor infusion rate
• Label insulin line with rate (units/volume)
• IV insulin is compatble with IV magnesium and oxytocin
• Mix and flush tubing and bag of insulin to prevent binding to plastic bag
• Obtain blood samples from arm opposite the infusion
• Glucose levels hourly during labor
• Have amp of D50 at bedside for hypoglycemia
• Use glucose-free solutions for boluses for hydration, anesthetics
• Before discontinuation of IV insulin, give SQ dose to prevent rebound hyperglycemia
• Insulin half lives – Regular IV – 5 min
– Regular IM – 2hr
– Regular SQ – 4hr
Insulin sensitivity factor – 1500 rule
• How much of a reduction in blood glucose should you expect for each 1.0 unit of insulin delivered to the patient
• 1500 rule
– Insulin sensitvity factor = 1500/TDI
– Ex – if TDI = 50units
• 1500/50 = 30mg/dL blood glucose drop per 1.0 unit of insulin
• To correct a patient’s blood glucose to 100mg/dL:
• Patient’s blood glucose -100 / 30 = Supplemental units of insulin
Example insulin sliding scale:• Blood glucose Insulin aspart (SQ units)
• <70 Hypoglycemia protocol
• 70-120 zero units
• 121-150 1 unit
• 151-200 2 units
• 201-250 3 units
• 251-300 4 units
• 301-350 5 units
• 351-400 6 units
• >400 7 units, call MD
Switching to subcutaneous insulin
and insulin pump• Patient should be tolerating a full diet
• Total daily dose needed after resolution of DKA
• Classic split – NPH and regular
– AM 2/3 total daily dose (2/3 NPH, 1/3 regular)
– PM 1/3 total daily dose (1/2 regular dinner, ½ NPH HS)
• NPH and humalog/novolog
– NPH (60%), 2/3 AM, 1/3 HS
– Novolog (40%), 1/3 with each meal
• Glargine/detimir & novolog/humalog
• If switching to pump – reduce TDI by 25%
– 50% basal dose / 24hr to get hourly basal rate
– 50% is bolus dose with meals (1/3 with each meal)
Insulin preparations & pharmacokineticsCreasy p977
Insulin Peak
onset (h)
Duration
(h)
Comments
Lispro
(Humalog)
1 2 OOA 10 min; no need to delay meal
intake
Aspart
(Novolog)
1 2 OOA 10 min; no need to delay meal
intake
Regular 2 4 Good coverage of individual meals if
injected 20 min preprandial;
postprandial hypoglycemia
NPH 4 8 Intermediate acting control, give upon
wakening and at bedtime, risk of 3AM
hypoglycemia
Glargine
(Lantus)
Detimir
(Levimir)
5 24 Less peak, limited pregnancy
experience, increased risk of nocturnal
hypoglycemia or undertreatment
during the day
Potassium administration• Anticipated potassium deficit in a pregnant patient with DKA is 5-10 meq/kg
• Replacement usually delayed for the first 2-4hr of therapy, since K+ is usually elevated until patient diureses has been established (at least 0.5cc/kg/h).
• Once IV fluids and insulin therapy are started serum K+ may drop quickly as a result of urinary loss and intracellular shift. When K+ is <5 and adequate diuresis has been established (0.5cc/kg/h) then K administration should begin
• 40-60meq KCl/liter of NS
• If K+ is ≥4, give 10-20meq
• If K+ is <4, give 30-40 meq
• Replace K cautiously, watching UOP and serum K+ frequently, every 4hr
• Replace entire K+ deficit (5-10meq/kg) over the span of the patient’s entire hospitalization
• Alternatively – with DKA induced maternal phosphate deficiency, K2PO4 (KPhos) may be given as K replacement instead of KCL
Bicarbonate therapy
• Only if arterial pH <6.9-7.0 and HCO3 < 5meq/L
• Rapid undiluted correction of metabolic acidosis with NaHCO3 is
unwarranted and may lead to severe hypokalemia, hypernatremia,
impaired oxygen delivery, and a paradoxical fall in CSF pH
• One ampule (44meq NaHCO3) is diluted in 1000mL of ½NS
• Total deficit of bicarbonate can be calculated (obtain the base
deficit on the ABG)
• Bicarb (meq) regained to fully correct metabolic acidosis = Base
deficit (meq/L) x patient weight (kg) / 4
• Since oxygen hemoglobin affinity is augmented in the presence of
an alkalotic shift of the oxygen-hemoglobin disassocation curve to
the left, it is prudent not to fully correct the patient’s metabolic
acidosis, ensuring better oxygen delivery to the fetus
Case
• 26 yo P2002, type 1 DM, with
nephropathy, LVH, and CHTN
• What is best treatment during
pregnancy?
• **1-Amlodipine (possible renal
protection)
• 2-Labetalol
• 3- Lisinopril
• *4- 1,2 (if a 2nd agent needed)
• 5-No treatment unless BP >180/110
Thyroid
Case
• 30 yo P1001 at 10 weeks with Grave’s
Disease
• What is recommended regarding her
antithyroid medications?
• 1 – No treatment
• 2- PTU in 1st trimester, methimazole in
2nd/3rd
• 3 – PTU throughout pregnancy
• 4 – Methimazole throughout pregnancy
Changes in Pregnancy - Thyroid gland enlarges; HCG
effect ; Free T4 concentrations – unchanged (0.7-1.8ng/dL);
Free T3 unchanged (2.3-4.2 pg/dL)
Thyroid storm
• Thyrotoxicosis – clinical and biochemical state
resulting from over-production and exposure to
thyroid hormone
– Most common cause – Grave’s disease
– T3 thyrotoxicosis – uncommon
• Thyroid storm – acute, severe exacerbation of
hyperthyroidism
Thyroid storm - Diagnosis
• Exacerbation of hyperthyroidism/thyrotoxicosis
– Common precipitants
– Heart failure from excessive thyroxine is more common in pregnant women
• Diagnosis is clinical
– Hypermetabolism - Fever, perspiration, warm, flushed skin
– Cardiovascular - Tachycardia, atrial fibrillation, CHF
– CNS - Irritability, agitation, tremor, mental status change (delirium, psychosis, coma)
– GI - Nausea, vomiting, diarrhea, jaundice
– Dehydration
• Supporting laboratory evidence
– Leukocytosis, elevated LFTs, hypercalcemia, low TSH, high free T4, and/or T3
Thyroid storm - Management
• Supportive measures while instituting
medical management (block, inhibit, block,
block)
• High M-F morbidity/mortality rate if
treatment is delayed
• Workup for inciting causes, maternal
echocardiography
Thyroid storm - Management
• ICU, medical management, supportive care
– Block, Inhibit, Block, Block
• IV fluids, electrolytes
• Cardiac monitoring
• Cooling measures (blanket, sponge bath, acetaminophen)
• Oxygen
• No salicylates (increased T4)
• NG tube if unable to swallow (may need for PTU)
• Consideration of PA catheter for central hemodynamic
monitoring to guide β-blocker therapy during
hyperdynamic cardiac failure
Thyroid storm
• BLOCK –
– Propylthiouracil – 1 gram PO or crushed in NG tube, then 200mg PO q 6 hrs
– blocks synthesis of T3 by BLOCKING conversion of T4 to T3
• Inhibit
• Block
• Block
Thyroid storm• Block
• INHIBIT – after 1 hour of initial PTU load (to prevent inadvertent release of T4 as a result of this therapy) – iodide is given to INHIBIT release of T4 and T3 by the thyroid gland– Na iodide 500-1000 IV q 8hr
– SSKI 5 drops PO q 8hr
– Lugol’s solution 10 drops PO q 8hr
– *Lithium carbonate 300mg q6hr (if history of iodine induced anaphylaxis)
• Block
• Block
Thyroid storm
• Block
• Inhibit
• BLOCK – Dexamethasone (or corticosteroid
equivalent) 2mg IV q6hr x 4 doses – this
therapy BLOCKS further peripheral
conversion of T4 to T3
• Block
Thyroid storm
• Block
• Inhibit
• Block
• BLOCK – beta-BLOCKERS
(propranolol 20mg PO/IV q 8hr;
labetalol 200 mg PO q 6hr) to treat
tachycardia (rate control of <120 bpm)
Thyroid storm• Treatment
• PTU – 1gm PO, then 200mg q6hr
• Sodium iodide 500 mg or 10gtts of oral Lugol’s
solution q 8 hrs – start 1 hr after PTU load to
inhibit thyroid release of T3 and T4
– if iodine allergy, give lithium carbonate 300mg q6hr
• Dexamethasone 2mg IV q6hr x4 to block
peripheral conversion of T4 to T3
• Labetalol 200mg po q8hr for HR >120
• Phenobarbital 300mg IV q8hr prn agitation
Thyroid storm
• Compliance is key
• Takes 4-6 weeks for TFTs to normalize
• PTU – common cause of hepatitis
Case
• 30 yo P1001 at 10 weeks with Grave’s
Disease
• What is recommended regarding her
antithyroid medications?
• 1 – No treatment
• **2- PTU in 1st trimester, methimazole in
2nd/3rd trimesters
• 3 – PTU throughout pregnancy (LFTs)
• 4 – Methimazole throughout pregnancy
Adrenal
Pheochromocytoma
• Rare tumor of catecholamine-secreting chromaffin cells (90% sporadic)
• Maternal mortality – 2% (16% in 1980),
• Fetal loss – 11% (26% in 1980), due to earlier diagnosis (83% diagnosed antenatally now vs 52% in 1980) – Ahlawat 1999, Hermayer 1999, Almog 2000
• Plasma metanephrines – best test – 99% sensitivity, 89% specificity
• Clonidine suppression test – helps distinguish between elevated blood levels of norepinephrine due to increased sympathetic nerve stimulation vs. due to pheochromocytoma
– Clonidine inhibits neurally mediated catecholamine release
– Clonidine given – then catecholamine levels are drawn; expect to see decrease in norepinephrine levels;
• If no decrease in NE levels (decrease by 50%, or minimal NE of 500pg/mL or less) then the catecholamines are coming from another source than neurally mediated (pheochromocytoma)
• MRI to localize the tumor – 90% of tumors arise in adrenal glands; after delivery – radioactive iodine-labeled metiodobenzylguanidine scintigraphy offers greater than 95% specificity in detection
Pheochromocytoma –
Symptoms/signs
• Symptomatic hypertension - severe,
fluctuating, paroxysmal
– HA, perspiration, palpitations, tachycardia
– Excessive truncal sweating
• Postural hypotension
• Different from preeclampsia – no
proteinuria, hyperuricemia, edema
Pheochromocytoma• Management
• Pharmacologic control of HTN and tachycardia
• Alpha adrenergic receptor blockade
• Phenoxybenzamine – 20mg BID and gradually increase (10mg qod) to max
dose (20-40mg bid/tid)
• Phentolamine 5-10mg IV/IM, reserved for emergency or preoperative
situations
• Prazosin – 1mg PO BID/TID, increase to max daily dose of 6-15mg divided in
BID/TID
• Labetalol – 100mg BID, increase by 100mg BID every 2 weeks, max
2400mg/day; if discontinuing, taper dose over 1-2 weeks
• IV boluses – 20mg IV over 2 minutes, increase by 20mg every 10min until
BP is controlled, max dose of 300mg IV acutely (within 6 hours)
• infusion – 2mg/min until BP control, switch to oral dosing – 200-400mg
every 6-12 hours
• Nitroprusside – 0.25micrograms/kg/min IV infusion to control BP; max
infusion rate is 10microgram/kg/min
• Metyrosine may be used if HTN is still uncontrolled
Pheochromocytoma• Beta blockade – use if tachycardia or arrhythmia, predominately adrenaline
secreting tumors; selective/short acting agents preferred
• *Use only after α-blockade has been started because unopposed α-adrenergic activity may lead to vasoconstriction and a marked increase in BP
• Metoprolol – 50-200mg BID PO
• Atenolol – 50mg PO every day and increase after 10-14 days to a max of 100mg every day
• Propranolol – only use if adequate alpha blockade has been started; 40mg PO BID, increase every 3-7 days to a max of 480mg daily, BID
• Fluid management
• Surgical management
• Timing depends on medical control, tumor size, risk of malignancy, stage of pregnancy (best in second trimester), laparoscopy vs laparotomy
• Third trimester – C/S after confirmation of lung maturity with adrenalectomy OR vaginal delivery and laparoscopic removal of the tumor postpartum
• Magnesium sulfate has been used (4g bolus, 2g/hr) has been used in nonpregnant patients for operative control during surgical removal of pheochromocytoma
Dildy p429
Beta blockers and drug users
• If cocaine use is suspected- avoid
labetalol as first line– potential for
coronary vasospasm/MI; unopposed
alpha blockade –controversial as
labetalol has beta and alpha blocking
effects
– Use nifedipine or hydralazine
• If methamphetamine use is suspected;
use – benzodiazepine (central blocking of
catecholamine release); nitroprusside,
NTG, phentolamine; hydralazine, CCB
Parathyroid gland
Hyperparathyroidism
• More common in women than men (3:1) ; Avg age - 55yo
• 145 cases reported during pregnancy
• Symptoms – weakness, fatigue, kidney stones, bone pain, pancreatitis, mental disturbances; most found incidentally
• Diagnosis – elevated levels of ionized calcium in the presence of elevated PTH
• Pregnancy changes –
– Majority of calcium is bound to albumin
– Reduced serum albumin levels in pregnancy
– Acquisition by the fetus of 25-30g of calcium
– Increase in GFR and the expanded extracellular fluid volume result in an overall decrease in total serum calcium levels by 0.5mg/dL
• Ionized calcium levels are not affected
• PTH levels stay the same or slightly decrease
• Primary hyperparathyroidism - ~90% due to parathyroid adenoma (9% with parathyroid hyperplasia, 2% parathyroid cancer)
• 20% have nephrolithiasis
Hyperparathyroidism• Definitive treatment - surgical removal of the glands
• 25% of asymptomatic patients have progressive disease (decrease of bone mass)
• Pregnancy – treat to reduce risk of neonatal tetany, miscarriage, stillbirth seen with maternal hypercalcemia; fetal testing
• Mithramycin and bisphosphonates contraindicated during pregnancy – C
• Asymptomatic. mild hypercalcemia – monitoring, surgery after pregnancy
• Symptomatic –
– If symptomatic and not a surgical candidate - Oral phosphate therapy1.5g/day TID; only if serum phosphate is <3mg/dL, phosphate administration should be adjusted to maintain serum phosphate <4mg/dL
– Furosemide – increases excretion of calcium in the urine, can be given orally to help decrease Ca2+
– Symptomatic patient, progressive, hypercalcemia (>12mg/dL) or if there is a deterioration of renal function – surgery by experienced parathyroid surgeon; do not defer because of the pregnancy if she is symptomatic and has hypercalcemia
• Hypercalcemia crisis – progressive hypercalcemia with hypovolemia, renal insufficiency, altered mentation, pancreatitis, seizures (can mimic eclampsia)
• Hydration with NS (2-3L over 3-6hr)
• Correct electrolyte abnormalities
• Furosemide (decreases distal tubular calcium reabsorption) 10-40mg IV every 2-4 hrs to maintain UOP at 200mL
• Calcium restriction
• Persistent hypercalcemia –
– Calcitonin (100-400 units/day), effective, tachyphylaxis occurs in 4-6 days
– Glucocorticoids –
• can decrease GI calcium absorption,
• dexamethasone 2mg IV q6hr
• hydrocortisone 100mg IV q8;
• prednisone 1mg/kg
• Neonatal hypocalcemia – predictable, preventable
• Transient neonatal tetany should not be associated with long-term sequelae
Hyperparathyroidism
Addisonian Crisis
Addisonian Crisis
• Incidence – rare during pregnancy
• Diagnosis – ACTH stimulation test
• Acute adreno-cortical insufficiency in pregnancy
• Can occur in pregnancy when a patient with chronic adrenal insufficiency is
stressed or in one who is undiagnosed
• May result from an OB complications that results in DIC, such as severe
preeclampsia or eclampsia, abruptio placenta, amniotic fluid embolus,
postpartum hemorrhage
• Can occur and cause an emergency
• Presents with n/v, abdominal pain, shock, frequently fatal (similar
presentation to acute pyelonphritis, gram negative bacillemia, fulminant
meningococcal infection (Waterhouse-Friderichsen syndrome)
• Early recognition
• Error by giving stress dose steroids
Normal Plasma Total and Free Cortisol, Urinary Free
Cortisol and ACTH Levels in Normal Pregnancy
Nonpregnant Third trimester
Total cortisol 0900 11.3 ± 3.5mg/mL
324 ± 100nmol/L
36.0 ± 7mg/mL
1029 ± 200nmol/L
Total cortisol 2400 3.6 ± 2.6 mg/mL
103 ± 76nmol/L
23.5 ± 4.3 mg/mL
470 ± 124nmol/L
Plasma free cortisol
0900
0.6±0.3 mg/mL
18 ± 9nmol/L
1.3 ± 0.4 mg/mL
32 ± 12 nmol/L
Plasma free cortisol
2400
0.2 ± 0.1mg/mL
6 ± 4 nmol/L
0.6 ± 0.2mg/mL
17 ± 5 nmol/L
Urinary free cortisol 4.7-9.5mg/day
13-256nmol/day
82.4-244.8mg/day
229-680nmol/day
Plasma ACTH 15-70pg/mL
3.3-15.4pmol/L
20-120pg/mL
4.4-26.4pmol/L
Foley p132
Addisonian Crisis• Treatment – IV bolus of hydrocortisone succinate 200mg
followed by 100mg hydrocortisone succinate in 1liter of NS over
30minutes; then put 100 mg of hydrocortisone succinate in each
liter of NS that is infused until the patient is adequately
hydrated; may take up to 5 liters
• Hypoglycemia may be prevented by instituting a 50-gm glucose
infusion
• Since the patient will receive up to 600mg of hydrocortisone
succinate with this protocol, no added mineralocorticoid is
needed
Conclusions
• Maternal stabilization
• DKA, if possibility – ABG, serum ketones
– If no urine ketones, no DKA
• Thyroid storm – block, inhibit, block,
block
• Fetal surveillance
• Compliance prevents complications
Misc
FFDNA per ACMG - 2016
End
• ???
• References:
• Foley MR, Strong TH, Garite TJ.
Obstetric Intensive Care Manual, 2nd Ed.
• Creasy R, Resnik R. Maternal-Fetal
Medicine Principles and Practice. 5th
Edition
• Uptodate.com online source.
Eclampsia
prophylaxis/treatment
Extra endo emergencies not
addressed Aug 2016 GR
Diabetes Insipidus
DI – Pregnancy Effect• 1 in 5000 deliveries
• Caused by abnormality in vasopressin secretion, an abnormality of vasopressin action
or vasopressin degradation
– Polydypsia, polyuria, dehydration, hypernatremia
• Central - caused by decreased production of vasopressin by the paraventricular nuclei
of the hypothalamus
– Pregnancy worsening of prior DI – *placenta vasopressinase (60% of DI worsens
during pregnancy)
• Subclinical central DI may be unmasked for the first time during pregnancy,
because the need for vasopressin release, low serum osmolality and because of
increased clearance of vasopressinase
– CNS tumor (e.g., prolactinoma), Granuloma (e.g., sarcoid), Histiocytosis X,
Aneurysm, Lymphocytic hypophysitis
– Sheehan syndrome
• Nephrogenic – X-linked abnormality of vasopressin V2 receptor
• Transient vasopressin resistant – increased vasopressinase activity due to decreased
vasopressinase degradation due to hepatic disease (e.g. AFLP, HELLP, hepatitis)
DI - Diagnosis• Diagnosis during pregnancy –
– Standard water deprivation test – do not use in
pregnancy because have to lose 5% of total body weight
before the induced dehydration adequately stimulates
vasopressin release; such dehydration can be dangerous
in pregnancy and should not be used
– Use of DDAVP as a test of urinary concentrating ability is
possible and is the preferred test in pregnancy; maximum
urine osmolality over the 11 hours after administration of
DDAVP is assessed ; any value > 700mosmol/kg is
considered normal and no DI is present; <700, ADH is
not being secreted or working on the kidney thus the
kidney produces hypotonic urine
DI Management• Treatment of central DI in pregnancy –
– DDAVP (2-20micrograms intranasally BID) – BID due to
diurnal/circadian rhythms
– DDAVP - not degraded by vasopressinase and no further
adjustment is needed in patients with increased vasopressinase
activity;
– Breast feeding - transfer of DDAVP to breast milk is minimal so
breast feeding is ok; treatment of central DI with DDAVP in
pregnancy does not pose any risk to the fetus/neonate
• Labor proceeds normally in women with central DI
– surges of oxytocin can be detected during labor and peurperium;
suggests that women with central DI, although vasopressinase
deficient, still secrete oxytocin normally;
• Lactation is not impaired
ADH slide
Hypothyroidism & Myxedema Coma• Hypothyroidism – inadequate thyroid hormone
production
• Myxedema coma – extreme hypothyroidism
• Medical emergency with 20-40% mortality rate
• Very rare in pregnancy
• Pregnancy changes – no significant change in
free T4 levels or free T3 levels
Myxedema coma - Diagnosis• Symptoms - Decreased mental status, hypothermia,
bradycardia, hyponatremia, hypoglycemia,
hypotension
• Lab - high serum TSH, low free T4 (<0.7-1.8ng/dL)
• Diagnosis - based on H&P, exclusion of other causes of
coma
• Evaluation for precipitating factors such as infection,
etc (similar to thyroid storm)
– Rule out MI, maternal echocardiogram
– Panculture and empiric antibiotics until culture results
are known
• Treatment- supportive measures similar to thyroid storm
– IV levothyroxine – 200-500mcg IV x1, give additional dose of 100-300mcg if no
response in 24 hr, continue 75-100 mcg IV daily until switched to PO (50-
200mcg/day)
• Cortiocosteroids to prevent adrenal insufficiency
– Draw baseline cortisol level
– 100mg hydrocortisone every 8 hr until baseline cortisol level is known, then
titrate accordingly
• Endotracheal intubation and ventilation – if hypercapnia (pCO2 >40mmHg) or
hypoxia (<70mmHg)
• Ordinary warming (normal blankets) –avoid external re-warming devices
• IV fluids and electrolytes and inotropic supportive therapy if required
• IV sodium if serum sodium <120 meq/L
• Liothyronine T3 replacement in young patients with low cardiovascular risk (more
likely than T4 to cause arrhythmias)
• Normal T4 levels are usually obtained in 24 hrs, then get increase in T3
• Hypotension, hypothermia, CO, mental status, etc improves in 24 hrs, further
improvement in 4-7 d
Myxedema coma - Management
Cardiovascular Changes
of Pregnancy
• Cardiac Output Increased by 30-50%
• Twin Pregnancy: Add another 15%
• Starts Early and Peaks at 20 Weeks
• Increase in Stroke Volume
• Increase in Heart Rate
• POTENTIAL MATERNAL COMPLICATIONS — Twin
pregnancy results in greater maternal hemodynamic changes than
singleton pregnancy. Women carrying twins have a 20 percent
higher cardiac output and 10 to 20 percent greater increase in
plasma volume than women with singleton pregnancy [176,177].
Although there is also a larger rise in red cell mass in twin
pregnancy, physiological anemia is common.
Sheehan syndrome p139, not
ER, but poss include as
complication of PPH• Diagnosis
• treatement
• Normal
pregnancy –
• Glucose
production
increases with
advancing
gestational age
Creasy Ch 46
• Normal pregnancy
–
• Insulin resistance
increases with
advancing
gestational age
Creasy Ch 46
Creasy Ch 46
• Normal pregnancy –
• Insulin response to glucose tolerance test
• Increases with advancing gestational age
Physiology in normal pregnancy
• A1C - Glycosylated hemoglobin lower in
pregnancy
– Mean blood glucose level is 20% lower in
pregnant women
– First 20 weeks – rise in red cell mass & slight
decrease in red cell life span
– <6 = <120
– >9 = >240Lurie S Mamet Y. Red blood cell survival and kinetics during
pregnancy. Eur J Obstet Gynecol Reprod Biol 2000;93:185.
Bunn HF, Haney DN, Kamin S, Gabbay KH, et al. The
biosynthesis of human hemoglobin A1C. Slow glycosylation of
hemoglobin in vivo. J Clin Invest 1976;57:1652.
Intrapartum Maternal Glycemic
Control
• Insulin Infusion Method
• Intermittent Subcutaneous Injection
Method
*An option for an insulin drip
• 500units of regular insulin/500cc normal saline (1unit/cc), start at
0.1 unit/kg/hr.
• Blood glucose
• <40 mg/dL – discontinue insulin, give glucose per 10gm IV
boluses (D50), give 20ml=10g, check glucose in next hour
• 40-60mg/dL – discontinue insulin, resume monitoring
• 61-80mg/dL – decrease insulin dose by 0.5 uniuts/hour
• 81-110mg/dL - no change
• 111-140mg/dL – increase rate by 0.5units/hour
• >140 incr rate by 2u/hr
• If blood glucose decreases by 50% or more, reduce insulin dose by
1/2, check blood glucose in 1 hour.
• If blood glucose does not decrease by 20%, increase the rate by
20%
Intrapartum diabetes management:
Blood glucose Novolog or Regular
insulin (units/hr) IV
IV fluids
<80 0 D5 1/2 NS at 100-125cc/hr
80-100 0.5 D5 1/2 NS at 100-125cc/hr
101-140 1 D5 1/2 NS at 100-125cc/hr
141-180 1.5 Normal saline
181-220 2.0 Normal saline
>220 2.5 Normal saline
Monitor q 2 hr for A2GDM, q 4 hr for A1GDM
May bolus 1-4 units of insulin (novolog or regular) as needed
Hold AM dose of medication (insulin or glyburide), NPO after MN the
night before
*Subcutaneous injections as option - intermittent subcutaneous injections
– regular insulin 2-5 units subcutaneously – goal is 80-120 mg/dL; ½ AM
Management principles
• Electrolyte replacement
– K+
– Check PO4 and magnesium
• Search and treat precipitating factor (infection)
• ICU
• Oxygen
• Left lateral position
• CEFM
• Monitor uop
Infant of a diabetic mother
• Neonatal metabolic complications
(hypoglycemia, hyperbilirubinemia,
hypocalcemia, hypomagnesemia,
erythremia)
Diabetes Insipidus
• Causes/changes in Pregnancy
• Central
– Pregnancy worsening of prior DI – *placenta vasopressinase
– CNS tumor (e.g., prolactinoma), Granuloma (e.g., sarcoid), Histiocytosis
X, Aneurysm, Lymphocytic hypophysitis
– Sheehan syndrome
• Nephrogenic – X-linked abnormality of vasopressin V2 receptor
• Transient vasopressin resistant – increased vasopressinase activity due to
decreased vasopressinase degradation due to hepatic disease (e.g. AFLP,
HELLP, hepatitis)
• During pregnancy – 60% of central DI worsens, 25% improve, 15% of cases
remain the same- vasopressinase increases in proportion to placental weight
Vasopressin (ADH)• Peptide (9AA)
• Half life 3-6 minutes
• Made in large cell bodies of hypothalamic magnocellular neurons in the
supraoptic nuclei
• Transported to posterior pituitary for storage, release with long axonal tracks
extending from hypothalamus to posterior pituitary (hypothalamohypophyseal
tract)
• Cleared by kidney
• Minimal crossing of placenta
• Vasoactive, maintains CV homeostasis in stress; high doses ADH elevates
venous pressure, decreases blood volume
• Fetal hypoxia, hemorrhage, hyperosmolarity stimulate release of ADH and
ADH levels in AF increase in pts with Rhesus isoimmunization
– High cord blood levels in IUGR, following fetal bradycardia, passage of
meconium; mediator of stress
– Maternal indomethacin therapy decreases fetal urinary flow rates as a
result of stimulation o circulating ADH levels and enhancement of
peripheral ADH effects in the fetus.
– Regulates lung liquid secretion by decreaseing the secretion rate in fetuses
and increasing lung liquid resorption in neonates
Nephrogenic DI
• Rare X-linked disorder
• 6 mutations in this gene have been identified for carrier
detection and early prenatal diagnosis
• Nonpregnant women with nephrogenic DI are usually
treated with thiazide diuretics or chlorpropamide;
chlorpropamide stimulates vasopressin release and enhances
its action on the renal tubule, but it may cause fetal
hypoglycemia and neonatal DI and should not be used in
pregnancy
• Thiazide diuretics are the treatment of choice for
nephrogenic DI in pregnancy
Transient Vasopressin
Resistant DI• Most common form of DI seen in pregnancy
• Caused by increased vasopressinase activity due either to
increased placental production of the enzyme or to
decreased hepatic vasopressinase metabolism as a result of
liver damage; transient disturbances of liver function may
be seen in AFLP, HELLP, hepatitis
• Treatment is with DDAVP b/c DDAVP is not degraded by
vasopressinase
• Electrolyte and fluid balance should be closely monitored
during the postpartum period
• Symptoms resolve shortly after delivery when liver function
returns to normal
Definitions
• Thyrotoxicosis – clinical and biochemical state resulting
from over-production and exposure to thyroid hormone
– Most common cause – Grave’s disease
– T3 thyrotoxicosis – uncommon
• Thyroid storm – acute, severe exacerbation of
hyperthyroidism
• Hypothyroidism – inadequate thyroid hormone production
• Myxedema coma – extreme hypothyroidism
• Thyroiditis – autoimmune inflammation of the thyroid
gland, may occur for first time postpartum
Changes in pregnancy• Thyroid gland enlarges
• First trimester TSH depression due to HCG, normalized thereafter
• Increased renal iodide clearance (increased GFR) and losses to fetus and placenta lead to decline in iodide
• Increased total serum T4 and total serum T3
• Normal serum free T4 (0.7-1.8ng/dL) and free T3
• Fetal thyroid gland begins concentrating iodine and synthesizing thyroid hormone after 10-12 weeks of gestation (before which is supplied by maternal supply)
– link of overt failure with pregnancy complications, intellectual impairment; not as strong with mild, subclinical disease
Common precipitants of thyroid
storm
• Acute surgical emergency
• Induction of anesthesia
• DKA
• Pulmonary embolism
• Noncompliance with antithyroid medications
• Myocardial infarction
• Infection
• Hypertension, preeclampsia
• Labor and delivery
• Severe anemia
• Extreme expression of severe
hypothyroidism in pregnancy
• Medical emergency with 20% mortality
rate
• Very rare in pregnancy
Myxedema coma
• Corticosteroids
• Draw baseline cortisol level
• 100mg hydrocortisone every 8 hr until baseline cortisol level is known, then titrate accordingly
• Levothyroxine sodium
• IV/NG tube- oral dose is 30-50% more than the IV dose
• Slow bolus IV dose 300-500 micrograms
• Daily IV doses of 75-100 micrograms
• Daily oral doses of 50-200 micrograms once patient is ambulatory
• Liothyronine T3 replacement in young patients with low cardiovascular risk (more likely than T4
to cause arrhythmias)
• Panculture and empiric antibiotics until culture results are known
• Normal T4 levels are usually obtained in 24 hrs, then get increase in t3
• Hypotension, hypothermia, CO, mental status, etc improves in 24 hrs, further improvement in 4-7
d
Myxedema coma - management
Corticotropin releasing hormone
(CRH)
• Polypeptide hormone and neurotransmitter involved in stress response
• 41 amino acids; released from paraventricularneurons as well as supraoptic and arcuate nuclei and limbic system in response to stress– Stimulates anterior pituitary release of ACTH,
stimulating release of cortisol by adrenal glands
• Placenta – determines in part gestation length, involved in parturition; rapid increase in levels at the onset of parturition acting as trigger; levels decline to nonpregnancy levels 24-48 hr after birth– Placental CRH Thought to regulate the fetal HPA axis
Primary Hyperaldosteronism• Rare cause of hypertension in pregnancy
• Diagnosis – high aldosterone, low renin
• Can be severe, confused with preeclampsia
• Can be variable and significantly worsen in the first 6 weeks postpartum
• Present with HTN, hypokalemia, elevated urinary potassium levels
• Biochemical diagnosis –
• Before making the biochemical diagnosis – hypokalemia should be corrected as
low potassium may supress aldosterone release
• When making the diagnosis – potassium replacement should be initiated, all
diuretcis should be discontinued for at least 2 weeks and high doses of beta
blockers should be reduced because they reduce renin production.
• Calcium channel blockers should not be used for 2-3 hours before testing
Primary Hyperaldosteronism• Physiologic increase of aldosterone levels occurs in pregnancy; the levels measured in
normal pregnancy are often within the primary hyperaldosteronism range
• Pregnant women may have less urinary potassium wasting than patients with primary
hyperaldosteronism b/c of the antagonizing effects of progesterone
• Diagnosis during pregnancy can be complicated by the increase in the plasma renin
levels in pregnancy
• In primary hyperaldosteronism - plasma renin levels are usually decreased and in
pregnancy the decrease may be attenuated
• Outside of pregnancy – the test is a salt-loading study to confirm the autonomous
secretion of aldosterone, but during pregnancy there are concerns about volume
overload, worsening of hypokalemia and the lack of specific ref ranges in pregnancy
• Test possible in pregnancy – prolonged upright posture position (which usually causes a
modest increase in plasma renin activity) but in primary hyperaldosteronism, the
plasma renin activity remains suppressed
Primary Hyperaldosteronism
• Ultrasound and MRI to localize the tumor in pregnancy
or CT as needed
• Adrenal adenoma if detected – preferred treatment is
unilateral adrenalectomy; successful cases in second
trimester have been reported
• Early delivery potentially needed in third trimester since
spironolactone and ACE inhibitors are avoided in
pregnancy
• Treatment goals – reduce BP, replace potassium and
while methyldopa, β-blockers and CCBs can be used,
success is variable
Adrenal corticotropin hormone
(ACTH)• 39 AA polypeptide hormone
• ½ life 10 minutes in human blood
• Released in response to stress
• ACTH - basophilic corticotrophs represent 20 percent of cells in anterior pituitary; ACTH is
product of proopiomelanocortin (POMC) gene;
• release controlled by CRH, ADH; glucocorticoids inhibit hypothalamic release of CRH and
pituitary to inhibit release of ACTH
• Stimulates cortex of adrenal gland to make and release corticosteroids (glucocorticoids,
androgens)
• Longterm stimulatory effects on expression of adrenal steroidogenic enzymes, the density of
LDL receptors and the rate of de novo adrenal cholesterol synthesis
• Enhances adrenal hypertrophy and hyperplasia by stimulating paracrine factors like IGF II
which induces adrenal cell division
• In absence of ACTH as in anencephaly, the fetal adrenal is reduced at 15 weeks, but admin of
ACTH provides tropic/trophic
• Seen in fetus by 8 weeks; pituitary corticotropes respond to CRH by 10 weeks
• Involution of adrenal cortex following parturition reflects normal reduction in plasma ACTH
once influence of elevated CRH is removed (assd with parturition)
Below is long version 2-10-11
Endocrine Emergencies in
Obstetrics
Darren Farley, MD
Clinical Assistant Professor
Division of Maternal-Fetal Medicine
Dept. of Obstetrics and Gynecology
University of Kansas School of Medicine – Wichita
• No financial interests to disclose.
OUTLINE
• Diabetic Ketoacidosis
• Thyrotoxicosis & Thyroid Storm
• Pheochromocytoma
• Addisonian Crisis
• Hypothyroidism & Myxedema Coma
• Diabetes Insipidus
• Primary Hyperparathyroidism
• Primary Hyperaldosteronism
• Pregnancy changes
• Diagnosis
• Management
Diabetic Ketoacidosis
Glucose physiology in pregnancy
• Glucose production increases with
advancing gestational age
• Insulin resistance increases with
advancing gestational age
• Insulin response to glucose tolerance test
- increases with advancing gestational age
Incidence of DKA
• Nonpregnant -
– 1-5 episodes per 100 patients / year
– Mortality 5-10%
• Complicates 2-9% of diabetic pregnancies
• A leading cause of fetal loss
• Fetal mortality rate
– 1963 – 50-90%
– Now – 10-20%
• Maternal mortality - now 1% (previously 15-
50%)
Foley p 143
DKA—signs/symptoms
Hyperventilation
Ketotic breath
Tachycardia
Hypotension
Dry MM
Disorientation
Coma
Polyuria
Polydipsia
N/V
Abdominal pain
Weakness
Weight loss
Factors precipitating DKA in
pregnancy
• Emesis
• Infection
• Non-compliance
• Insulin pump failure
• ß-sympathomimetic drugs
• Steroids
• Poor management
• PE
Diagnosis
• DKA -
• D –Diabetic - >180mg/dL
• K –serum acetone, Ketones 1:2 or greater
• A –Acidosis – arterial pH<7.3, HCO3-
<15, anion gap [Na – (Cl +HCO3)] >12
Management
• Maternal Resuscitation– IV fluids
– Insulin
– Search for underlying cause – infection, noncompliance, etc
– I/Os, monitoring glucose (q1-2hr),
– ABG, pH, anion gap, electrolytes (q2-4hr)
– Fetal monitoring*• Withhold intervention toward delivery on behalf of the
fetus until maternal metabolic disturbances are corrected
• Oxygen and correct maternal positioning while correcting disturbances
Management -
• Fluid replacement
– Fluid deficit is 100cc/kg (7-10L for total deficit)
• Accurate I/Os, BUN, Creatinine
• Replace 75% of deficit in 1st 24 hrs, remainder over the hospitalization
– NS (use isotonic solution to prevent rapid decline in plasma osmolarity and resultant cellular swelling and cererbral edema)
– 1L NS in first hour, 500 mL/hr hours 2 and 3 (NS 1st 3 hrs)
– LR or ½ NS at 250cc/hr in initial 24 hr until 75% of volume deficit is replaced
• LR is used to avoid further acidosis (LR pH 6.5, vs 5.0 of NS)
• Sodium load with NS – possible hypernatremia, switch to LR or ½ NS if Na >150meq/L
Insulin (0.1)
• Insulin therapy (inhibits lipolysis and ketogenesis, leads to suppression of hepatic glucose production)
– Loading dose 0.1U/kg regular insulin
• 50 units / 500 mL NS (1cc = 0.1units, 10 cc = 1unit)
– Infusion 0.1units/kg/hour
– If plasma glucose does not decrease by 10% in first hour or by 20% in second hour – repeat loading dose or double infusion rate
– When glucose ~250mg/dL or less, add D5 to the fluids and reduce the hourly rate by 1/2
– Continue infusion of insulin until serum bicarbonate and anion gap normalize
*An option for an insulin drip• 500units of regular insulin/500cc normal saline (1unit/cc), start at
0.1 unit/kg/hr.
• Blood glucose
• <40 mg/dL – discontinue insulin, give glucose per 10gm IV
boluses (D50), give 20ml=10g, check glucose in next hour
• 40-60mg/dL – discontinue insulin, resume monitoring
• 61-80mg/dL – decrease insulin dose by 0.5 uniuts/hour
• 81-110mg/dL - no change
• 111-140mg/dL – increase rate by 0.5units/hour
• >140 incr rate by 2u/hr
• If blood glucose decreases by 50% or more, reduce insulin dose by
1/2, check blood glucose in 1 hour.
• If blood glucose does not decrease by 20%, increase the rate by
20%
Insulin• Use regular insulin
• Pump monitor infusion rate
• Label insulin line with rate (units/volume)
• IV insulin is compatble with IV magnesium and oxytocin
• Mix and flush tubing and bag of insulin to prevent binding to plastic bag
• Obtain blood samples from arm opposite the infusion
• Glucose levels hourly during labor
• Have amp of D50 at bedside for hypoglycemia
• Use glucose-free solutions for boluses for hydration, anesthetics
• Before discontinuation of IV insulin, give SQ dose to prevent rebound hyperglycemia
• Insulin half lives – Regular IV – 5 min
– Regular IM – 2hr
– Regular SQ – 4hr
Insulin sensitivity factor – 1500 rule
• How much of a reduction in blood glucose should you expect for each 1.0 unit of insulin delivered to the patient
• 1500 rule
– Insulin sensitvity factor = 1500/TDI
– Ex – if TDI = 50units
• 1500/50 = 30mg/dL blood glucose drop per 1.0 unit of insulin
• To correct a patient’s blood glucose to 100mg/d:
• Patient’s blood glucose -100 / 30 = Supplemental units of insulin
Example insulin sliding scale:• Blood glucose Insulin aspart (SQ units)
• <70 Hypoglycemia protocol
• 70-120 zero units
• 121-150 1 unit
• 151-200 2 units
• 201-250 3 units
• 251-300 4 units
• 301-350 5 units
• 351-400 6 units
• >400 7 units, call MD
Switching to subcutaneous insulin
and insulin pump• Patient should be tolerating a full diet
• Total daily dose needed after resolution of DKA
• Classic split – NPH and regular
– AM 2/3 total daily dose (2/3 NPH, 1/3 regular)
– PM 1/3 total daily dose (1/2 regular dinner, ½ NPH HS)
• NPH and humalog/novolog
– NPH (60%), 2/3 AM, 1/3 HS
– Novolog (40%), 1/3 with each meal
• Glargine/detimir & novolog/humalog
• If switching to pump – reduce TDI by 25%
– 50% basal dose / 24hr to get hourly basal rate
– 50% is bolus dose with meals (1/3 with each meal)
Insulin preparations &
pharmacokinetics Creasy p977
Insulin Peak onset
(h)
Duration
(h)
Comments
Lispro
(Humalog
)
1 2 OOA 10 min; no need to delay meal
intake
Aspart
(Novolog)
1 2 OOA 10 min; no need to delay meal
intake
Regular 2 4 Good coverage of individual meals if
injected 20 min preprandial;
postprandial hypoglycemia
NPH 4 8 Intermediate acting control, give upon
wakening and at bedtime, risk of 3AM
hypoglycemia
Glargine
(Lantus)
Detimir
5 24 Less peak, limited pregnancy
experience, increased risk of nocturnal
hypoglycemia or undertreatment
Potassium administration• Anticipated potassium deficit in a pregnant patient with DKA is 5-10 meq/kg
• Replacement usually delayed for the first 2-4hr of therapy, since K+ is usually elevated until patient diureses has been established (at least 0.5cc/kg/h).
• Once IV fluids and insulin therapy are started serum K+ may drop quickly as a result of urinary loss and intracellular shift. When K+ is <5 and adequate diuresis has been established (0.5cc/kg/h) then K administration should begin
• 40-60meq KCl/liter of NS
• If K+ is ≥4, give 10-20meq
• If K+ is <4, give 30-40 meq
• Replace K cautiously, watching UOP and serum K+ frequently, every 4hr
• Replace entire K+ deficit (5-10meq/kg) over the span of the patient’s entire hospitalization
• Alternatively – with DKA induced maternal phosphate deficiency, K2PO4 (KPhos) may be given as K replacement instead of KCL
Bicarbonate therapy
• Only if arterial pH <6.9-7.0 and HCO3 <
5meq/L
• Rapid undiluted correction of metabolic
acidosis with NaHCO3 is unwarranted
and may lead to severe hypokalemia,
hypernatremia, impaired oxygen
delivery, and a paradoxical fall in CSF
pH
Infant of a diabetic mother
• Neonatal metabolic complications
(hypoglycemia, hyperbilirubinemia,
hypocalcemia, hypomagnesemia,
erythremia)
Diabetes Insipidus
Diabetes Insipidus• Causes in Pregnancy
• Central
– Pregnancy worsening of prior DI
– CNS tumor (e.g., prolactinoma)
– Granuloma (e.g., sarcoid)
– Histiocytosis X
– Aneurysm
– Lymphocytic hypophysitis
– Sheehan syndrome
• Neprhogenic – X-linked abnormality of vasopressin V2 receptor
• Transient vasopressin resistant – increased vasopressinase
activity due to decreased vasopressinase degradation due to
hepatic disease (e.g. AFLP, HELLP, hepatitis)
Diabetes Insipidus• Caused by abnormality in vasopressin secretion, an abnormality of vasopressin action
or vasopressin degradation
• Polydypsia, polyuria, dehydration
• Central – caused by decreased production of vasopressin by the paraventricular nuclei
of the hypothalamus
• 1 in 5000 deliveries
• Most commonly presents before conception arising from a pituitary tumor or another
invasive disease such as histiocytosis X
• Often worsens during pregnancy due to an increase in the clearance of endogenous
vasopressin by placental vasopressinase
• Vasopressinase concentration increases during pregnancy in proportion to the placental
weight
• Vasopressinase is Metabolized by the liver, thus increased in liver disease
• Subclinical central DI may be unmasked for the first time during rpegnancy, because
the need for vasopressin release, low serum osmolality and because of increased
clearance of vasopressinase
• During pregnancy – 60% of central DI worsens, 25% improve, 15% of cases remain the
same
Diabetes Insipidus
• Diagnosis during pregnancy – seen following development of Sheehan
syndrome and as a result of the enlargement of a prolactinoma,
histiocytosis X, and lymphocytic hypophysitis, and complication of
ventriculoperitoneal shunt during pregnancy
• Standard water deprivation test – do not use in pregnancy b/c have to
lose 5% of total body weight before the induced dehydration adequately
stimulates vasopressin release; such dehydration can be dangerous in
pregnancy and should not be used
• Use of DDAVP as a test of urinary concentrating ability is possible and is
the preferred test in pregnancy; maximum urine osmolality over the 11
hours after administration of DDAVP is assessed ; any value >
700mosmol/kg is considered normal and no DI is present; <700, ADH is
not being secreted or working on the kidney thus the kidney produces
hypotonic urine
Diabetes Insipidus
• Treatment of central DI in pregnancy – DDAVP (2-20micrograms
intranasally BID) due to diurnal/circadian rhythms; can be given
IV after cesarean but IV dosing is 5-20fold more potent than the
intranasal spray and the does should be adjusted accordingly,
therefore just give intranasally; DDAVP is not degraded by
vasopressinase and no further adjustment is needed in patients
with increased vasopressinase activity; transfer of DDAVP to
breast milk is minimal so breast feeding is ok; treatment of central
DI with DDAVP in pregnancy does not pose any risk to the
fetus/neonate
• Labor proceeds normally in women with central DI; surges of
oxytocin can be detected during labor and peurperium; suggests
that women with central DI, although vasopressinase deficient, still
secrete oxytocin normally; lactation is not impaired
Vasopressin (ADH)• Peptide (9AA)
• Half life 3-6 minutes
• Made in large cell bodies of hypothalamic magnocellular neurons in the
supraoptic nuclei
• Transported to posterior pituitary for storage, release with long axonal tracks
extending from hypothalamus to posterior pituitary (hypothalamohypophyseal
tract)
• Cleared by kidney
• Minimal crossing of placenta
• Vasoactive, maintains CV homeostasis in stress; high doses ADH elevates
venous pressure, decreases blood volume
• Fetal hypoxia, hemorrhage, hyperosmolarity stimulate release of ADH and
ADH levels in AF increase in pts with Rhesus isoimmunization
– High cord blood levels in IUGR, following fetal bradycardia, passage of
meconium; mediator of stress
– Maternal indomethacin therapy decreases fetal urinary flow rates as a
result of stimulation o circulating ADH levels and enhancement of
peripheral ADH effects in the fetus.
– Regulates lung liquid secretion by decreaseing the secretion rate in fetuses
and increasing lung liquid resorption in neonates
Nephrogenic DI
• Rare X-linked disorder
• 6 mutations in this gene have been identified for carrier detection
and early prenatal diagnosis
• Nonpregnant women with nephrogenic DI are usually treated
with thiazide diuretics or chlorpropamide; chlorpropamide
stimulates vasopressin release and enhances its action on the renal
tubule, but it may cause fetal hypoglycemia and neonatal DI and
should not be used in pregnancy
• Thiazide diuretics are the treatment of choice for nephrogenic DI
in pregnancy
Transient Vasopressin
Resistant DI
• Most common form of DI seen in pregnancy
• Caused by increased vasopressinase activity due either to
increased placental production of the enzyme or to
decreased hepatic vasopressinase metabolism as a result of
liver damage; transient disturbances of liver function may
be seen in AFLP, HELLP, hepatitis
• Treatment is with DDAVP b/c DDAVP is not degraded by
vasopressinase
• Electrolyte and fluid balance should be closely monitored
during the postpartum period
• Symptoms resolve shortly after delivery when liver function
returns to normal
Thyroid
Changes in pregnancy• Thyroid gland enlarges
– Goiter-minimal in regions of iodine deficiency; 30% increase in size in regions with dietary iodine deficiency
• First trimester TSH depression due to HCG, normalized thereafter
• Increased renal iodide clearance (increased GFR) and losses to fetus and placenta lead to decline in iodide
• Increased total serum T4 and total serum T3
• Normal serum free T4 (.7-1.8ng/dL) and free T3
– estrogen-mediated increase in circulating levels of TBG (major transport protein for thyroid hormone)
• fetal thyroid gland begins concentrating iodine and synthesizing thyroid hormone after 10-12 weeks of gestation (before which is supplied by maternal supply)
– link of overt failure with pregnancy complications, intellectual impairment; not as strong with mild, subclinical disease
Definitions
• Thyrotoxicosis – clinical and biochemical state resulting from
over-production and exposure to thyroid hormone
– Most common cause in preg is Grave’s disease (autoimmune
condition, production of thyroid-stimulating
immunoglobulin (TSI) and thyroid-stimulating hormone
binding inhibitory immunoglobulin (TBII) that act on TSH
receptor to mediate thyroid stimulation or inhibition or both
• Thyroid storm – acute, severe exacerbation of hyperthyroidism
• Hypothyroidism – inadequate thyroid hormone production
• Myxedema coma – extreme hypothyroidism
• Thyroiditis – autoimmune inflammation of the thyroid gland,
may occur for first time postpartum
– Usually painless, may present at de novo hypothyroidism,
transient thyrotoxicosis, initial hyperthyroidism followed by
hypothyroidism within 1 yr postpartum
Free T4 concentrations remain within nonpregnant reference
range (0.7-1.8ng/dL) throughout pregnancy
Thyrotoxicosis & Thyroid Storm
Thyroid storm
Thyroid storm
• Exacerbation of hyperthyroidism/thyrotoxicosis
• Heart failure from excessive thyroxine is more common in pregnant women
• Diagnosis is clinical
• Hypermetabolism - Fever, perspiration, warm, flushed skin
• Cardiovascular - Tachycardia, atrial fibrillation, CHF
• CNS - Irritability, agitation, tremor, mental status change (delirium, psychosis, coma)
• GI - Nausea, vomiting, diarrhea, jaundice
• Dehydration
• Supporting laboratory evidence
– Leukocytosis, elevated LFTs, hypercalcemia, low TSH, high free T4, and/or T3
Common precipitants of thyroid
storm
• Acute surgical emergency
• Induction of anesthesia
• DKA
• Pulmonary embolism
• Noncompliance with antithyroid medications
• Myocardial infarction
• Infection
• Hypertension, preeclampsia
• Labor and delivery
• Severe anemia
Thyroid storm
• Medical management coordinated with supportive
measures in intensive care unit setting
• IV fluids, electrolytes
• Cardiac monitoring
• Cooling measures (blanket, sponge bath, Tylenol)
• Oxygen therapy with serial ABGs if oxygenation is an issue
• No salicylates (increased T4)
• NG tube if patient is unable to swallow (may need for PTU
admin described next)
• Consideration of PA catheter for central hemodynamic
monitoring to guide β-blocker therapy during
hyperdynamic cardiac failure)
Thyroid storm
• Supportive measures while instituting
medical management (block, inhibit, block,
block)
• Workup for inciting causes, maternal
echocardiography
Thyroid storm
• Treatment
• PTU – 1gm PO, then 200mg q6hr
• Sodium iodide 500 mg or 10gtts of oral Lugol’s
solution q 8 hrs – start 1 hr after PTU load to
inhibit thyroid release of T3 and T4
– if iodine allergy, give lithium carbonate 300mg q6hr
• Dexamethasone 2mg IV q6hr x4 to block
peripheral conversion of T4 to T3
• Labetalol 200mg po q8hr for HR >120
• Phenobarbital 300mg IV q8hr prn agitation
Thyroid storm
• Admit to intensive care unit, L & D
• BLOCK –
– Propylthiouracil – 1 gram PO or crushed in NG tube, then 200mg PO q 6 hrs
– blocks synthesis of T3 by BLOCKING conversion of T4 to T3
• Inhibit
• Block
• Block
Thyroid storm
• Block
• INHIBIT – after 1 hour of initial PTU load (to prevent inadvertent release of T4 as a result of this therapy) – iodide is given to INHIBIT release of T4 and T3 by the thyroid gland– Na iodide 500-1000 IV q 8hr
– SSKI 5 drops PO q 8hr
– Lugol’s solution 10 drops PO q 8hr
– *Lithium carbonate 300mg q6hr (if history of iodine induced anaphylaxis)
• Block
• Block
Thyroid storm
• Block
• Inhibit
• BLOCK – Dexamethasone (or
corticosteroid equivalent) 2mg IV q6hr x
4 doses – this therapy BLOCKS further
peripheral conversion of T4 to T3
• Block
Thyroid storm
• Block
• Inhibit
• Block
• BLOCK – beta-BLOCKERS
(propranolol 20mg PO/IV q 8hr;
labetalol 200 mg PO q 6hr; esmolol) to
treat tachycardia (rate control of <120
bpm)
Hypothyroidism & Myxedema Coma
Myxedema coma
• Symptoms = Decreased mental status, Hypothermia,
Bradycardia, Hyponatremia, Hypoglycemia, Hypotension,
Precipitating illness
• Lab - high serum TSH, low free T4 (<.7-1.8ng/dL)
• Diagnosis = based on H&P, exclusion of other causes of
coma
• Evaluation – workup of precipitating factors such as
infection, etc (similar to thyroid storm)
• Mortality rate = 30-40%
• Treatment- supportive measures similar to thyroid storm
– IV levothyroxine – 200-500mcg IV x1, give additional
dose of 100-300mcg if no response in 24 hr, continue 75-
100 mcg IV daily until switched to PO
• Extreme expression of severe
hypothyroidism in pregnancy
• Medical emergency with 20% mortality rate
• Very rare in pregnancy
Myxedema coma
• Tx –
• Supportive
• Cortiocosteroids to prevent adrenal insufficiency
• Endotracheal intubation and ventilation – if hypercapnia (pCO2 >40mmHg) or
hypoxia (<70mmHg)
• Ordinary warming (normal blankets) –avoid external re-warming devices
• IV fluids and electrolytes and inotropic supportive therapy if required
• IV sodium if serum sodium <120 meq/L
• Cardiac monitoring
• ECG, troponin and CPK levels to rule out MI
• BP monitoring
• Corticosteroids
Myxedema coma
• Corticosteroids
• Draw baseline cortisol level
• 100mg hydrocortisone every 8 hr until baseline cortisol level is known, then titrate accordingly
• Levothyroxine sodium
• IV/NG tube- oral dose is 30-50% more than the IV dose
• Slow bolus IV dose 300-500 micrograms
• Daily IV doses of 75-100 micrograms
• Daily oral doses of 50-200 micrograms once patient is ambulatory
• Liothyronine T3 replacement in young patients with low cardiovascular risk (more likely than T4
to cause arrhythmias)
• Panculture and empiric antibiotics until culture results are known
• Normal T4 levels are usually obtained in 24 hrs, then get increase in t3
• Hypotension, hypothermia, CO, mental status, etc improves in 24 hrs, further improvement in 4-7
d
Myxedema coma - management
Hyperparathyroidism
• More common in women than men (3:1)
• Avg age dx 55yo
• 145 cases reported during pregnancy
• Symptoms – weakness, fatigue, kidney stones, bone pain, pancreatitis, mental disturbances; most found incidentally
• Diagnosis – elevated levels of ionized calcium in the presence of elevated PTH
• Majority of calcium is bound to albumin; reduced serum albumin levels in pregnancy, acquisition by the fetus of 25-30g of calcium, increase in GFR and the expanded extracellular fluid volume result in an overall decrease in total serum calcium levels by 0.5mg/dL
• Ionized calcium levels are not affected
• PTH levels stay the same or slightly decrease
• Primary hyperparathyroidism - ~90% due to parathyroid adenoma (9% with parathyroid hyperplasia, 2% parathyroid cancer)
• 20% have nephrolithiasis
Hyperparathyroidism
• Definitive treatment is surgical removal of the glands
• Only 25% of asymptomatic patients have progressive disease (decrease of bone mass)
• Treat during pregnancy to reduce risk of neonatal tetany, miscarriage and stillbirth seen with maternal hypercalcemia; fetal testing
• Mithramycin and bisphosphonates contraindicated during pregnancy –details of why*****
• If asymptomatic with mild hypercalcemia – monitoring acceptable with surgery after pregnancy
• If symptomatic and not a surgical candidate - Oral phosphate therapy1.5g/day TID; only if serum phosphate is <3mg/dL, phosphate administration should be adjusted to maintain serum phosphate <4mg/dL
• Furosemide – increases excretion of calcium in the urine, can be given orally to help decrease Ca2+
• Symptomatic pt, progressive, hypercalcemia (>12mg/dL) or if there is a deterioration of renal function – surgery by experienced parathyroid surgeon; do not defer because of the pregnancy if she is symptomatic and has hypercalcemia
• Hypercalcemia crisis
• Hypercalcemia crisis – progressive hypercalcemia with hypovolemia, renal insufficiency, altered mentation, pancreatitis, seizures (can mimic eclampsia
• -hydration with NS (2-3L over 3-6hr)
• -correct electrolyte abnormalities
• -furosemide (decreases distal tubular calcium reabsorption) 10-40mg IV every 2-4 hrs to maintain UOP at 200mL
• -calcium restriction
• -persistent hypercalcemia –
• calcitonin (100-400 units/day), effective, tachyphylaxis occurs in 4-6 days
• Glucocorticoids – can decrease GI calcium absorption, dexamethasone 2mg IV q6hr; hydrocortisone 100mg IV q8; prednisone 1mg/kg
• Neonatal hypocalcemia – predictable, preventable
• Transient neonatal tetany should not be associated with long-term sequelae
Hyperparathyroidism
Adrenal
Pheochromocytoma
• Rare tumor of catecholamine-secreting chromaffin cells
• Most pheochromocytomas occur sporadically-90%, 10% occur as part of a syndrome
• Maternal mortality – 2% (16% in 1980), fetal loss – 11% (26% in 1980), due to earlier diagnosis (83% diagnosed antenatally now vs 52% in 1980) – Ahlawat 1999, Hermayer 1999, Almog 2000
• Plasma metanephrines – best test – 99% sensitivity, 89% specificity
• Clonidine suppression test – helpful in distinguishing beteween elevated blood levels of norepinephrine due to increased sympathetic nerve stimulation from that due to pheochromocytoma; clonidine inhibits neurally mediated catecholamine release; after an overnight fast, a heparin lock is placed at least 30min prior to baseline levels being drawn; plasma catecholamine levels are sampled at baseline and hourly for 3 hours after the patient is given clonidine (0.3mg per 70kg body weight)
• normal response is a decrease of >50% in plasma norepinephrine levels or minimal norepinephrine of 500pg/mL or less
• false positives can occur if pt on diuretics and particularly tricyclic antidepressants
• MRI to localize the tumor – 90% of tumors arise in adrenal glands; after delivery –radioactive iodine-labeled metiodobenzylguanidine scintigraphy offers greater than 95% specificity in detection
Pheochromocytoma –
Symptoms/signs
• Symptomatic hypertension - severe,
fluctuating, paroxysmal
– HA, perspiration, palpitations, tachycardia
– Excessive truncal sweating
• Postural hypotension
• Different from preeclampsia – no
proteinuria, hyperuricemia, edema
Pheochromocytoma• Management
• Pharmacologic control of HTN and tachycardia
• Alpha adrenergic receptor blockade
• Phenoxybenzamine – 20mg BID and gradually increase (10mg qod) to max
dose (20-40mg bid/tid)
• Phentolamine 5-10mg IV/IM, reserved for emergency or preoperative
situations
• Prazosin – 1mg PO BID/TID, increase to max daily dose of 6-15mg divided in
BID/TID
• Labetalol – 100mg BID, increase by 100mg BID every 2 weeks, max
2400mg/day; if discontinuing, taper dose over 1-2 weeks
• IV boluses – 20mg IV over 2 minutes, increase by 20mg every 10min until
BP is controlled, max dose of 300mg IV acutely (within 6 hours)
• infusion – 2mg/min until BP control, switch to oral dosing – 200-400mg
every 6-12 hours
• Nitroprusside – 0.25micrograms/kg/min IV infusion to control BP; max
infusion rate is 10microgram/kg/min
• Metyrosine may be used if HTN is still uncontrolled
Pheochromocytoma
• *Beta blockade – use if tachycardia or arrhythmia, predominately adrenaline secreting tumors; selective/short acting agents preferred
• *Use only after α-blockade has been started because unopposed α-adrenergic activity may lead to vasoconstriction and a marked increase in BP
• Metoprolol – 50-200mg BID PO
• Atenolol – 50mg PO every day and increase after 10-14 days to a max of 100mg every day
• Propranolol – only use if adequate alpha blockade has been started; 40mg PO BID, increase every 3-7 days to a max of 480mg daily, BID
• Fluid management
• Surgical management
• Timing depends on medical control, tumor size, risk of malignancy, stage of pregnancy (best in second trimester), laparoscopy vs laparotomy
• Third trimester – C/S after confirmation of lung maturity with adrenalectomy OR vaginal delivery and laparoscopic removal of the tumor postpartum
• Magnesium sulfate has been used (4g bolus, 2g/hr) has been used in nonpregnant patients for operative control during surgical removal of pheochromocytoma
Dildy p429
Addisonian Crisis
Adrenal corticotropin hormone
(ACTH)• 39 AA polypeptide hormone
• ½ life 10 minutes in human blood
• Released in response to stress
• ACTH - basophilic corticotrophs represent 20 percent of cells in anterior pituitary;
ACTH is product of proopiomelanocortin (POMC) gene;
• release controlled by CRH, ADH; glucocorticoids inhibit hypothalamic release of
CRH and pituitary to inhibit release of ACTH
• Stimulates cortex of adrenal gland to make and release corticosteroids
(glucocorticoids, androgens)
• Longterm stimulatory effects on expression of adrenal steroidogenic enzymes, the
density of LDL receptors and the rate of de novo adrenal cholesterol synthesis
• Enhances adrenal hypertrophy and hyperplasia by stimulating paracrine factors
like IGF II which induces adrenal cell division
• In absence of ACTH as in anencephaly, the fetal adrenal is reduced at 15 weeks,
but admin of ACTH provides tropic/trophic
• Seen in fetus by 8 weeks; pituitary corticotropes respond to CRH by 10 weeks
• Involution of adrenal cortex following parturition reflects normal reduction in
plasma ACTH once influence of elevated CRH is removed (assd with parturition)
Normal Plasma Total and Free Cortisol, Urinary Free
Cortisol and ACTH Levels in Normal Pregnancy
Nonpregnant Third trimester
Total cortisol 0900 11.3 ± 3.5mg/mL
324 ± 100nmol/L
36.0 ± 7mg/mL
1029 ± 200nmol/L
Total cortisol 2400 3.6 ± 2.6 mg/mL
103 ± 76nmol/L
23.5 ± 4.3 mg/mL
470 ± 124nmol/L
Plasma free cortisol
0900
0.6±0.3 mg/mL
18 ± 9nmol/L
1.3 ± 0.4 mg/mL
32 ± 12 nmol/L
Plasma free cortisol
2400
0.2 ± 0.1mg/mL
6 ± 4 nmol/L
0.6 ± 0.2mg/mL
17 ± 5 nmol/L
Urinary free cortisol 4.7-9.5mg/day
13-256nmol/day
82.4-244.8mg/day
229-680nmol/day
Plasma ACTH 15-70pg/mL
3.3-15.4pmol/L
20-120pg/mL
4.4-26.4pmol/L
Foley p132
Addisonian Crisis
• Incidence –
• Diagnosis-
• Acute adreno-cortical insufficiency in pregnancy
• Can occur in pregnancy when a patient with chronic adrenal insufficiency is
Massive bilateral adrenal hemorrhage stressed or in one who is undiagnosed
• May result from an OB complications that results in DIC, such as severe
preeclampsia or eclampsia, abruptio placenta, amniotic fluid embolus,
postpartum hemorrhage
• can occur and cause an emergency
• Presents with n/v, abdominal pain, shock, frequently fatal (similar
presentation to acute pyelonphritis, gram negative bacillemia, fulminant
meningococcal infection (Waterhouse-Friderichsen syndrome)
• Early recognition
Addisonian Crisis• Treatment – IV bolus of hydrocortisone succinate 200mg
followed by 100mg hydrocortisone succinate in 1liter of NS over
30minutes; then put 100 mg of hydrocortisone succinate in each
liter of NS that is infused until the patient is adequately
hydrated; may take up to 5 liters
• Hypoglycemia may be prevented by instituting a 50-gm glucose
infusion
• Since the patient will receive up to 600mg of hydrocortisone
succinate with this protocol, no added mineralocorticoid is
needed
Corticotropin releasing hormone
(CRH)• Polypeptide hormone and neurotransmitter involved in
stress response
• 41 amino acids; released from paraventricular neurons as well as supraoptic and arcuate nuclei and limbic system in response to stress– Stimulates anterior pituitary release of ACTH, stimulating
release of cortisol by adrenal glands
• Placenta – determines in part gestation length, involved in parturition; rapid increase in levels at the onset of parturition acting as trigger; levels decline to nonpregnancylevels 24-48 hr after birth– Placental CRH Thought to regulate the fetal HPA axis
Primary Hyperaldosteronism• Rare cause of hypertension in pregnancy
• Diagnosis – high aldosterone, low renin
• Can be severe, confused with preeclampsia
• Can be variable and significantly worsen in the first 6 weeks postpartum
• Present with HTN, hypokalemia, elevated urinary potassium levels
• Biochemical diagnosis –
• Before making the biochemical diagnosis – hypokalemia should be corrected as
low potassium may supress aldosterone release
• When making the diagnosis – potassium replacement should be initiated, all
diuretcis should be discontinued for at least 2 weeks and high doses of beta
blockers should be reduced because they reduce renin production.
• Calcium channel blockers should not be used for 2-3 hours before testing
Primary Hyperaldosteronism
• Physiologic increase of aldosterone levels occurs in pregnancy; the levels measured in
normal pregnancy are often within the primary hyperaldosteronism range
• Pregnant women may have less urinary potassium wasting than patients with primary
hyperaldosteronism b/c of the antagonizing effects of progesterone
• Diagnosis during pregnancy can be complicated by the increase in the plasma renin
levels in pregnancy
• In primary hyperaldosteronism - , plasma renin levels are usually decreased and in
pregnancy the decrease may be attenuated
• Outside of pregnancy – the test is a salt-loading study to confirm the autonomous
secretion of aldosterone, but during pregnancy ther are concerns ab out volume
overload, worsening of hypokalemia and the lack of specific ref ranges in pregnancy
• Test possible in pregnancy – prolonged upright posture position (which usually causes a
modest increase in plasma renin activity) but in primary hyperaldosteronism, the
plasma renin activity remains suppressed
Primary Hyperaldosteronism
• Ultrasound and MRI to localize the tumor in pregnancy
or CT as needed
• Adrenal adenoma if detected – preferred treatment is
unilateral adrenalectomy; successful cases in second
trimester have been reported
• Early delivery potentially needed in third trimester since
spironolactone and ACE inhibitors are avoided in
pregnancy
• Treatment goals – reduce BP, replace potassium and
while alphamethyldopa, b blockers and CCBs can be
used, success is variable