kina m. merwin mcdougall endocrinology pgy4 western university
TRANSCRIPT
![Page 1: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/1.jpg)
Endocrine Emergencies: Adrenal Crisis
Kina M. Merwin McDougallEndocrinology PGY4Western University
![Page 2: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/2.jpg)
EMS called for 21 ♀ w/ confusion, fever, SOB and abdominal pain. Cough and malaise for several days prior.
PHx: Fetal Alcohol Syndrome (group home) Asthma BMI 34
Meds: Salbutamol prn
Case History
![Page 3: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/3.jpg)
Febrile: 38.9 Hypotension: 78/50 Tachycardia: 125 Tachypnea: 35 Hypoxic: O2 Sat 87% Disoriented and very anxious
Acetaminophen given EMS bolused 2L NS Combivent Nebs & 15L O2 by NRB
Case: EMS
![Page 4: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/4.jpg)
Vitals: T 38.8, BP 84/52, HR 125, Sat 89%, BG 7 Patient becoming combative & taking O2 off
Intubation Midazolam & Fentanyl (large doses required) SBP 60: peripheral dopamine & RL under pressure
Central line inserted & norepinephrine added CXR: bilateral lower lobe infiltrates Ceftriaxone, Levofloxacin & Tamiflu started
Case: In the Emergency Room
![Page 5: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/5.jpg)
21 ♀ with pneumonia & septic shock Intubated and on pressors with SBP 90 Fighting ventilator on high-dose
midazolam and fentanyl infusions so propofol added
Initial labs: ABG 7.24|51|72|20 Lactate 3.7
Case: ICU Consult
133 102 7.13.2 21 135
14.1 102 248 Acute respiratory acidosis & metabolic acidosis: respiratory
fatigue & sepsis
![Page 6: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/6.jpg)
Brought to ICU immediately On stretcher-bed transfer, sheets noted
to be wet and bloody Rapid physical exam found a tense
abdomen and vaginal bleeding Nurse notes that abdomen is
alternating between tense and soft
“Obstetric 25 to MSICU!”
Case: ICU Overnight
![Page 7: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/7.jpg)
45 minutes later ~ 24wk boy delivered NICU Our patient:
Ongoing hypoxia CXR white-out ARDS PEEP ladder initiated
Ongoing hypotension norepi & dopamine infusions Resolving hemorrhage after 2u PRBC & oxytocin
Group home collateral: 19 yo boyfriend lives in same group home Pregnancy unknown but boyfriend’s mother offering
adoption for the baby Another group home resident known swab +ve for
H1N1
Case: ICU Overnight
![Page 8: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/8.jpg)
Case: ICU Morning Rounds Nurse reports:
Insulin infusion never initiated D5W up-titrated to 175cc/hr for BG 4 to 6 BG now 3.7 (last ABG: glucose 3.5)
Attending says You’re going into endocrinology; what
should we do about her blood sugar?▪ Amp of D50 BG 4.3▪ Change maintenance fluid to D10W
![Page 9: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/9.jpg)
Case: Hypoglycemia
DDx in ill patient: Medications:
▪ Insulin or oral glycemic medications▪ Quinolones
Critical illness Cortisol deficiency Insulinoma or nonislet cell tumour
Severe Sepsis vs Adrenal Crisis+/- Levofloxacin
✗
✗
?✓✓
![Page 10: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/10.jpg)
Objectives
1. Define adrenal crisis 2. Discuss epidemiology & frequency3. Review the causes of adrenal crisis 4. Examine the pathophysiology5. Outline how to make the diagnosis6. Delineate management7. Summarize complications
![Page 11: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/11.jpg)
What is adrenal crisis? Acute adrenal insufficiency/failure Life-threatening condition due to insufficient
adrenal (stress) hormones to mount an appropriate response to stresses like an
infection
Adrenal Crisis
![Page 12: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/12.jpg)
Adrenal Anatomy
![Page 13: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/13.jpg)
Mineralocorticoids
Glucocorticoids
Androgens
Catecholamines
Adrenal Function
McGraw Hill
![Page 14: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/14.jpg)
Zona glomerulosa Zona fasciculata Zona reticularisCHOLESTEROL
17 -a Hydroxy-pregnenolone
Dehydroepi-androsterone DHEA
Pregnenolone
17 -a Hydroxy-progesterone AndrostenedioneProgesterone
11-DeoxycortisolDeoxycorticosterone
CortisolCorticosterone
Aldosterone
![Page 15: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/15.jpg)
Zona glomerulosa Zona fasciculata Zona reticularisCHOLESTEROL
17 -a Hydroxy-pregnenolone
Dehydroepi-androsterone DHEA
Pregnenolone
17 -a Hydroxy-progesterone AndrostenedioneProgesterone
11-DeoxycortisolDeoxycorticosterone
CortisolCorticosterone
Aldosterone
11β Hydroxylase
21 Hydroxylase
17α - hydroxylase
Aldo Synthase
![Page 16: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/16.jpg)
100-150 mcg/day
C: 10-20 mg/dayA: > 20 mg/day
![Page 17: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/17.jpg)
Hypothalamic-Pituitary-Adrenal Axis
Hypothalamus
Anterior Pituitary
Adrenal Cortex
CRH
+
ACTH
+
Systemic
Effects
Cortisol
_
_
+
Circadian RegulationStress: physical, emotional, illness
![Page 18: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/18.jpg)
Systemic Glucocorticoid Effects
![Page 19: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/19.jpg)
Epidemiology of Adrenal Crisis
Rare: episode reported by 42% of chronic Chronic Primary Adrenal Insufficiency:
Prevalence: 93-144 cases/million Incidence: 4.4-6 new cases/million/year ♀ > ♂ but near 1:1 Any age: most frequently 30-50years
Chronic Central Adrenal Insufficiency: Prevalence: 150-280 cases/million ♀ > ♂ Any age: most frequently 50’s
![Page 20: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/20.jpg)
Etiology of Adrenal Crisis
1. Steroid withdrawal Exogenous formulations Adrenalectomy Drug-induced: ketoconazole, etomidate, rifampin, anti-epileptics
2. Acute exacerbation of chronic insufficiency Sepsis Surgical stress
3. Pituitary trauma Head injury Surgical intervention or irradiation Hemorrhage or infarct Infection/Infiltration
4. Bilateral adrenal hemorrhage Antiphospholipid Antibody Syndrome Anticoagulants Malignancy Septic Waterhouse-Friderichsen Syndrome (menigiococcemia: Neisseria)
![Page 21: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/21.jpg)
Primary Adrenal Insufficiency: Adult Etiology
Autoimmune 80% of cases in developed countries 60% associated with autoimmune
polyendocrinopathy syndromesTuberculosis
Leading cause historically Still top cause in endemic areas
![Page 22: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/22.jpg)
Primary Adrenal Insufficiency: Etiology
Autoimmune Infection:
tuberculosis, fungal, viral Iatrogenic
predominately via cytochrome P450 mechanisms Hemorrhage Metastatic malignancy:
lung, stomach, breast, colon Infiltration:
lymphoma, amyloidosis, hemochromatosis Genetic:
Congenital adrenal hyperplasia, Adrenoleukodystrophy, Familial glucocorticoid deficiency or ACTH-insensitivity
![Page 23: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/23.jpg)
Central Adrenal Insufficiency: Etiology
Secondary (Pituitary) Trauma & Space-occupying Lesions
▪ Tumors▪ Surgery & Irradiation▪ Infection & Infiltration▪ Apoplexy & Sheehan’s Syndrome
Genetic▪ Prader-Willi Syndrome▪ Mutations of transcription factors involved in pituitary
development Tertiary (Hypothalmus)
Trauma & Space-occupying Lesions▪ As above
Drug-induced
![Page 24: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/24.jpg)
Central Adrenal Insufficiency: Etiology
Drug-induced: Corticosteroids (secondary AI)
▪ <10mg pred/day for 2wks Ketoconazole (primary AI) Etomidate (primary AI)
▪ only one dose required Megesterol acetate (secondary AI)
▪ progestin w/ mild glucocorticoid activity Rifampin (increased cortisol metabolism) Phenytoin (increased cortisol metabolism) Metyrapone (primary AI) Mitotane (primary AI) Opioids (secondary & tertiary AI)
![Page 25: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/25.jpg)
Symptoms & SignsC
harm
andari
et
al. L
ance
t. 2
01
4 Jun 2
1;3
83
(99
35
):2
15
2-
67
![Page 26: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/26.jpg)
Biochemical Presentation
Charmandari et al. Lancet. 2014 Jun 21;383(9935):2152-67
![Page 27: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/27.jpg)
Adrenal Crisis
![Page 28: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/28.jpg)
NEVER withhold treatment while making the diagnosis!
Suspicious history & physical Initial investigations:
Random Cortisol < 400nmol/L very suggestive if critically ill ACTH TSH & fT4 Blood cultures and other labs as indicated
Diagnostic: ACTH stimulation test ACTH 250mcg IV Baseline ACTH & cortisol, then cortisol @ 30 & 60min Excludes insufficiency if cortisol doubles & > 550nmol/L Can be normal in ACUTE central insufficiency
Diagnose Adrenal Insufficiency
![Page 29: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/29.jpg)
Primary Central
Baseline Cortisol Low Low
Baseline ACTH High Low to low Normal
Stimulated Cortisol Low Acute: HighChronic: Low
Diagnose Adrenal Insufficiency
![Page 30: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/30.jpg)
Treatment: Emergency
ABCs & treat precipitant illness
New diagnosis: Dexamethasone 4mg IV while arranging ACTH stim
▪ Unless critically ill Then Hydrocortisone 100 mg IV q6-8h for dual mineralocorticoid and
glucocorticoid effect Correct fluid deficit with D5NS to avoid hypoglycemia BP should start responding in 4-6hrs if dx correct After 24hrs, reduce to HC 50mg IV q6h, then start taper
Chronic condition: Crisis: Hydrocortisone 100 mg IV q6-8h Stress: Double or triple baseline dose to prevent adrenal crisis After 24hrs, reduce to HC 50mg IV q6h, then start taper Continue stress dosing for minimum of 48-72h
![Page 31: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/31.jpg)
Steroid Comparison
Drug Half life Equivalent anti-inflammatory dose mg
Relative mineralocorticoid potency
Short acting 8-12 h
Cortisone 25 2
Hydrocortisone 20 2
Intermediate acting
18-36 h
Methylprednisolone 4 0
Prednisolone 5 1
Prednisone 5 1
Long acting 36-54 h
dexamethasone 0.75 0
Mineralocorticoid
fludrocortisone 12-24 h 10 125
![Page 32: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/32.jpg)
21 ♀ with ARDS (?H1N1) Preterm delivery @ 26wks w/ hemorrhage
requiring 2u PRBCs Intubated with high dose midazolam &
fentanyl infusions. Weaning propofol Norepi & dopamine to keep SBP 90 D10W at 100cc/hr to keep BG>6
What are you concerned about?Adrenal Crisis 2° Sheehan’s
Critical Illness Adrenal Hemorrhage
Back to Case
![Page 33: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/33.jpg)
Adrenal Crisis
![Page 34: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/34.jpg)
Cortisol, ACTH, Prolactin, TSH, fT4 pending
Hydrocortisone 100mg IV q8h Learned not to use Dexamethasone in ICU 2008 Critical Care Guidelines
MRI pituitary arranged for afternoon Endocrinology consulted
Case Management
![Page 35: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/35.jpg)
Guideline Rational
2008 Joint Recommendations: Society of Critical Care Medicine European Society of Intensive Care Medicine
ICU conditions associated with adrenal failure: Shock Severe CAP Trauma Head injury Burns Liver failure Pancreatitis Post-operatively with cardiac surgery Brain dead organ donors After etomidate use
![Page 36: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/36.jpg)
Guideline Rational
>90% bound to CBG & a little to albumin
CBG falls in acute illness by 50% Substantially increases free cortisol Measurement of total cortisol decreased
T1/2 of cortisol is 70-120 minutes No cortisol stored in adrenal gland Acute illness should up-regulate HPA
system Deficiency anywhere in HPA system
results in decreased cortisol
![Page 37: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/37.jpg)
Dysfunction of HPA Axis
Reported prevalence of adrenal insufficiency Critically ill patients: 10-20% Septic shock: up to 60%
Mechanisms of dysfunction are poorly understood Decreased production of CRH, ACTH and cortisol Systemic Inflammation-Associated
Glucocorticoid Resistance▪ Dysfunction of CRH, ACTH and cortisol receptors▪ Multifactorial▪ Receptors down regulated by inflammatory cytokines
± structural damage to adrenal gland
![Page 38: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/38.jpg)
Guidelines
1. “CIRCI” – Critical Illness-Related Corticosteroid Insufficiency
2. Avoid terms “absolute” and “relative” adrenal insufficiency in context of critical illness
3. Diagnosis of adrenal insufficiency best made by a delta cortisol of <9 μg/dL (248nmol/L) after 250μg cosyntropin or random total cortisol <10μg/dL (276nmol/L) (grade 2B)
4. Free cortisol not recommended (grade 2B)5. ACTH stimulation test should not be used to
identify patients with septic shock or ARDS who should receive glucocorticoids
Marik et al. Crit Care Med 2008 Vol 36, No 6. 1937-1949
![Page 39: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/39.jpg)
ACTH Stimulation Test
Delta cortisol <248 nmol/L has been shown to be an important prognostic marker in ICU
Studies in septic shock showed rapid shock reversal in patients treated with GC regardless of ACTH stim. test result
Stim test Down-falls: Doesn‘t assess adequacy of stress cortisol levels Doesn’t assess HPA axis integrity Currently no way to measure tissue cortisol
resistance Poorly reproducible, especially in septic shock
![Page 40: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/40.jpg)
Guidelines
6. Consider hydrocortisone in the management strategy of septic shock, particularly those patients who respond poorly to fluid resuscitation and vasopressor agents (2B)
Evidence:▪ 6 RCT of HC 200-300mg/day in septic shock▪ Meta-analysis:
▪ Greater shock reversal at day 7▪ No mortality benefit▪ Not statistically significant higher rate of secondary
infections
![Page 41: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/41.jpg)
Guidelines
7. Consider moderate dose GC in the management of early severe ARDS (PaO2/FiO2 < 200) and before day 14 in un-resolving ARDS (2B)
Role of GC in acute lung injury and less severe ARDS is not yet clear
No exact dose recommendation, as studies used doses from 200 to 750mg HC equivalence/day
Associated with improved PaO2/FiO2, reduction of days on mechanical vent and days in ICU
![Page 42: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/42.jpg)
Guidelines
8. In septic shock, give IV hydrocortisone in a dose of 200 mg/d in four divided doses or as a bolus of 100 mg followed by a continuous infusion of 10mg/hr (240mg/d) (Grade 1B) Option in ARDS to give 1mg/kg/day of
methylprednisolone as a continuous infusion
Doses > 300mg/day of HC not recommended Increased myopathy & super infections
Continuous infusions give better glycemic control
![Page 43: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/43.jpg)
Guidelines
9. Optimal duration of GC treatment unclear
Septic shock should be treated for ≥7 days before taper ▪ assuming no residual signs of sepsis or shock
Early ARDS should be treated for ≥14 days before taper (2B)
![Page 44: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/44.jpg)
Guidelines
10. GC treatment should be tapered slowly and not stopped abruptly (2B)11. Treatment with fludrocortisone (50μg PO OD) is optional (2B)12. Dexamethasone is not recommended for treatment of septic shock or ARDS (1B)
Secondary significant suppression of HPA axis
? Lack of mineralocorticoid effect
![Page 45: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/45.jpg)
Cortisol: 170 nmol/L (275-550 nmol/L @ 8) ACTH: 2.3 pmol/L (2.2-13 pmol/L @ 8) TSH: 0.09 mU/L (0.2-3 mU/L in 2nd T) Free T4: 6 pmol/L (10-23 pmol/L) Prolactin: 8 mcg/L (35-600 mcg/L @ term)
FSH & LH: suppressed in pregnancy Estrogen: high in pregnancy
MRI:
Case Results
Normal
![Page 46: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/46.jpg)
HPA Axis Physiology
CBG is increased in high-estrogen states Pregnancy Oral contraceptive Liver disease
Rise in CBG elevates total plasma cortisol Threefold rise in total cortisol by pregnancy week 26 Adrenals hyper-responsive to ACTH ACTH and free cortisol levels also higher in
pregnancy No stigmata of high cortisol 2° anti-
glucocorticoid effect of elevated progesterone in pregnancy
![Page 47: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/47.jpg)
HPA Axis Physiology
Case pt’s cortisol quite low for pregnancy & illness
ACTH should also be higher Low cortisol, low ACTH = central
insufficiency MRI was normal Fentanyl 50 mcg/hr
▪ Known HPA axis suppression
![Page 48: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/48.jpg)
Opiate Effect on HPA Axis
Hypothalamus
Anterior Pituitary
Adrenal Cortex
CRH
+
ACTH
+
Systemic
Effects
Cortisol
_
_
Opiates
_
_
_
+
?
![Page 49: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/49.jpg)
Thyroid Physiology
TSH normal ranges by trimester: 1st: 0.1 to 2.5 mU/L 2nd: 0.2 to 3.0 mU/L 3rd: 0.3 to 3.0 mU/L
“Sick Euthyroid Syndrome”
![Page 50: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/50.jpg)
Thyroid Physiology
![Page 51: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/51.jpg)
Prolactin Physiology
Prolactin should be rising as pregnancy advances
Prolactin should be low in Sheehan’s Our pt’s prolactin was low MRI was normal
Dopamine suppresses prolactin Highest infusion rate: 1000 mcg/min
![Page 52: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/52.jpg)
Case Conclusion
Pressor & glucose requirements dropped on hydrocortisone
H1N1 positive with severe ARDS CT Abdo ruled out adrenal hemorrhage Transferred to community ICU: final adrenal dx
unknown Baby boy survived for two weeks. Respiratory failure
Multifactorial Hypoglycemia: Critical Illness vs Adrenal Insufficiency Low cortisol & ACTH: Opiates vs ICU vs AI Thyroid dysfunction: Pregnancy vs ICU vs dopamine
▪ Dopamine can suppress TSH secretion Prolactin: High-dose dopamine suppression
![Page 53: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/53.jpg)
Acute Management
ABCs Labs: lytes, glucose, cortisol, ACTH Fluid resuscitation: D5NS bolus 2-3L,
then maintenance infusion as appropriate
Hydrocortisone 100mg IV q6-8h Dexamethasone closely followed by ACTH
stim if not critically ill. Then hydrocortisone. Simultaneous management of inciting
illness If Primary AI, start fludrocortisone
0.1mg PO once NS infusion not required
![Page 54: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/54.jpg)
Chronic Management
Hydrocortisone 10-20mg after waking & 5-10mg in early afternoon
Alternate regimens:▪ Hydrocortisone TID (symptomatic between
doses)▪ Prednisone dose typically 3.5-5 mg daily▪ Dexamethasone 0.25-0.5 mg once daily
Normal liver function required to activate cortisone & prednisone
Adjust dose to symptoms
![Page 55: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/55.jpg)
Adequacy of Replacement
Scoring: For each sign or symptom present, add one point if suggestive of
over-replacement or subtract one point if suggestive of under replacement.
Scores between -2 to +2 reflect good replacement
![Page 56: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/56.jpg)
No simple recipe to establish a dose Titrate to symptom improvement:
fatigue, nausea, energy, illness, hospitalizations
Tailor timing: night shifts, avoidance of sleep disturbance
Avoid over-replacement: BMI, central obesity, stretch marks, osteopenia, HTN
Adequacy of Replacement
![Page 57: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/57.jpg)
Further Testing
Prolonged ACTH stimulation Cortisol rapidly peaks in primary Cortisol continues to rise throughout stim in central
Insulin tolerance test Gold standard Administer regular insulin until hypoglycemic (2.2) Induces stress response Adequate response is serum cortisol > 500 nmol/L
Metyrapone Inhibits 11 beta hydroxylase
CRH stimulation test Differentiates primary/secondary/tertiary AI
![Page 58: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/58.jpg)
Other Hormones in Primary
Aldosterone Replace with Fludrocortisone 0.1mg daily 0.025 to 0.2 mg daily - titrate to BP & edema Dose may change with season or exercise Monitor sodium, potassium & plasma renin activity
DHEA Insufficient evidence for routine supplementation No evidence in males In females, DHEA therapy suggested only for
significantly impaired mood or sense of well-being despite optimal glucocorticoid and mineralocorticoid replacement
![Page 59: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/59.jpg)
Stress Dosing of Steroids
Minor febrile illness or stress 2-3x GC for 3 days. No change to MC
Hospitalization or Surgery Moderate: Hydrocortisone 50mg PO BID. Rapid
taper Severe: Hydrocortisone 100mg IV q8h. Taper w/
recovery Severe stress or trauma
Emergency kit: dexamethasone 4mg IM Medic Alert and Emergency card in wallet
Identify as steroid dependent
![Page 60: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/60.jpg)
The Details
Educate, educate, educate Patient self-advocacy
Calcium & Vit D supplementation Screen for osteoporosis as appropriate
Drug interactions anticonvulsants, anti-retrovirals, rifampin dose adjustments likely required
Pregnancy May require dose increase of 5-10 mg by 3rd trimester Labor: adequate saline hydration & hydrocortisone 2 mg
IV q6h Delivery or prolonged labour: hydrocortisone 100mg IV
q6h or infusion After delivery: taper rapidly to maintenance within 3 days
![Page 61: Kina M. Merwin McDougall Endocrinology PGY4 Western University](https://reader035.vdocuments.net/reader035/viewer/2022062221/56649c9e5503460f9495ebc8/html5/thumbnails/61.jpg)
Questions?
References available upon request