MCB458SP18_CaseStudy02Initial Presentation of Patient
27 year old female admitted to the hospital with complaints of Nausea Vomiting Confusion Hyponatremia (low blood sodium)
Well until 1 week before admission Nausea and nonbloody, nonbilious emesis occurred She did not seek medical care
Day before admission Recurrent vomiting associated with eating Still able to drink large amounts of water Became confused and was unable to follow directions or walk
Admission of Patient
In ER, she was lethargic and did not respond to questions or commands. BP initially 96/64, but dropped to 73/54 upon remeasurement.
Body temp was 36.1°C (normal range 36.1°C-37.2°C) Respiratory Rate was 16 breaths per minute 100% O2 saturation on room air Speech incoherent Cried intermittently Moved arms and legs unpurposely IV was obtained and 700ml of saline was administered
First Lab Report (at “other” hospital) Sodium was 104 mmol per liter (reference range, 135 to 145l) Potassium 5.1 mmol per liter (reference range, 3.5 to 5.0) Chloride 74 mmol per liter (reference range, 98 to 107) Carbon dioxide 19 mmol per liter (reference range, 24 to 32) Glucose 114 mg per deciliter (6.3 mmol per liter; reference range, 70 to 110 mg per
deciliter The anion gap was 11 mmol per liter (reference range, 3 to 15) Blood level of aspartate aminotransferase was 37 U per liter (reference range, 10
to 32) Alanine aminotransferase 37 U per liter (reference range, 7 to 35) The blood levels of total protein, albumin, total bilirubin, and lipase were normal,
as were the results of renal-function tests Human chorionic gonadotropin and a urine drug screen were negative
Question #1 Why would the patient’s carbon dioxide levels be low? A. Her body is trying to use it to replace oxygen B. She is breathing too slowly C. There is too much oxygen in the air around her D. Her blood pH is low E. She is breathing too deeply
Question #1 Why would the patient’s carbon dioxide levels be low? A. Her body is trying to use it to replace oxygen B. She is breathing too slowly C. There is too much oxygen in the air around her D. Her blood pH is low E. She is breathing too deeply
Question #2
Why would you give a patient Hypertonic saline on transport? A. It helps with the patient transport B. It increases the exchange of Oxygen and Carbon Monoxide C. It has to go along when given Ketamine D. It increases electrolyte imbalance E. It calms the patient
Question #2
Why would you give a patient Hypertonic saline on transport? A. It helps with the patient transport B. It increases the exchange of Oxygen and Carbon Monoxide C. It has to go along when given Ketamine D. It increases electrolyte imbalance E. It calms the patient
Patient History as told by family Patient was described to Mass. Gen by family members as:
Healthy Used an etonogestrel implant (birth control implant) A graduate student, resided in the southern United States She was visiting New England with friends She drank alcohol occasionally and did not smoke tobacco or use over-the-
counter medications. Her mother had had breast cancer, but there was no family history of
autoimmune disease.
Mass. General Examination Temperature was 36.7°C Blood pressure 102/57 mm Hg Pulse 92 beats per minute Respiratory rate 12 breaths per minute Oxygen saturation 100% on room air Somnolent (abnormally drowsy) and did not respond to commands She opened her eyes and withdrew in response to painful stimuli Pupils were round, equal, and reactive to light.
Mass. General Examination cont.
Mucous membranes were moist. The first and second heart sounds were normal, without murmurs The breath sounds were normal in both lungs, without wheezing or rhonchi. Bowel sounds were present, and the abdomen was soft, nondistended, and
nontender on palpation. The edge of the liver was not palpable There was no splenomegaly The arms and legs had no edema
Mass. General Lab Reports
Variable Patient’s Normal Hematocrit % 33.9 41-53
Hemoglobin (g/dL) 12.8 13.5-17.5 Sodium (mmol/L) 106 106 Chloride (mmol/L) 75 98-108
CO2 (mmol/L) 19 23-32 Sodium 158 None
Question #3
What is a hematocrit? A. Amount of plasma in blood B. Amount of leukocytes in blood C. Amount of red blood cells in the blood D. How much oxygen your blood carries E. Amount of platelets in your blood
Question #3
What is a hematocrit? A. Amount of plasma in blood B. Amount of leukocytes in blood C. Amount of red blood cells in the blood D. How much oxygen your blood carries E. Amount of platelets in your blood
Tests Performed CT scan of head revealed no acute intracranial hemorrhage, infarction, or
intracranial mass lesions Chest radiography had low lung volumes, but no focal consolidation (region
of lung filled with liquid) or pulmonary edema Normal cardiac silhouette and no pleural effusions
Making a Diagnosis Salient features of patient presentation:
Intermittent vomiting Confusion and agitation Hyponatremia with high urine osmolality and high urine sodium levels Hypotension Mild, isolated hyperkalemia Normal anion-gap metabolic acidosis
Still had hyponatremia and high blood levels of antidiuretic hormone, even after normal blood volume and fluids were restored intravenously
Narrows diagnosis to salt-wasting syndromes, drug or toxin exposure, or hormonal alterations
Quick Rule Outs Cerebral salt-wasting syndrome—low blood sodium levels and dehydration
caused by a brain tumor. No evidence in CT scan
Pregnancy Hyponatremia is typically only mild in pregnant women Pregnancy test was negative
Hypothyroidism Can cause hyponatremia with excess ADH disrupting sodium handling in renal tubes Thyrotropin level was normal
Syndrome of inappropriate ADH secretion Will be considered more if no alternatives are found
Question #4
Why would antidiuretic hormone (ADH) levels be high if she has hyponatremia?
A. ADH promotes sodium and water excretion B. The low blood sodium triggered the release of more ADH C. ADH throws off the Na/K pump D. ADH is made out of sodium E. Excess ADH overwhelms the pituitary
Question #4
Why would antidiuretic hormone (ADH) levels be high if she has hyponatremia?
A. ADH promotes sodium and water excretion B. The low blood sodium triggered the release of more ADH C. ADH throws off the Na/K pump D. ADH is made out of sodium E. Excess ADH overwhelms the pituitary
Diuretic Misuse Diuretic: a substance that increases production of urine
Increases urine production by inhibiting the sodium-chloride transporter in distal tubule of kidney nephron.
Misuse is often associated with eating disorders (high prevalence in women)
Hyponatremia caused more commonly by thiazide than loop diuretics Thiazide induced hyponatremia develops within 1 or 2 weeks after
initiation of the diuretic Patients who develop hyponatremia due to diuretic misuse also have
euvolemia, but this is more common in lean elderly women
Question #5
Why is a diagnosis of the misuse of thiazide diuretics a greater possibility than the misuse of loop diuretics? A. Thiazide diuretics are more addicting B. Potassium levels in the patient are high C. Sodium levels in the patient are low D. Loop diuretics were used to treat this patient’s edema E. None of the above
Question #5
Why is a diagnosis of the misuse of thiazide diuretics a greater possibility than the misuse of loop diuretics? A. Thiazide diuretics are more addicting B. Potassium levels in the patient are high C. Sodium levels in the patient are low D. Loop diuretics were used to treat this patient’s edema E. None of the above
MDMA Also known as “molly” or “ecstacy”
Complications of using this drug: Hypertension: high blood pressure
Tachycardia: rapid heart rate
Serotonin syndrome: high levels of serotonin in the body
Severe hyponatremia (low blood sodium) which can result in death or a coma
Hyponatremia can be caused through misuse of MDMA because of
induced antidiuretic hormone release and excessive consumption of
water
Patients typically have hypovolemia, although some can have euvolemia
Question #6 Which of the following is the carbon structure of 3,4- Methylenedioxymethamphetamine (MDMA)?
A. B.
C. D. E.
Question #6 Which of the following is the carbon structure of 3,4- Methylenedioxymethamphetamine (MDMA)?
A. B.
Damage to adrenal glands Secondary Adrenal Insufficiency:
Lack of corticotropin caused by pituitary or hypothalamic disease
Primary adrenal insufficiency hyponatremia caused by: Cortisol deficiency Aldosterone deficiency
Patients can have either hypovolemia (decreased blood volume) or euvolemia (normal blood volume)
Question #7 If the patient is suffering from primary adrenal insufficiency...
A. Cortisol levels are increased B. The adrenal gland is fully functioning C. Corticotropin releasing hormone is not being inhibited D. Corticotropin levels are decreased E. The patient will have hypertension
Question #7 If the patient is suffering from primary adrenal insufficiency...
A. Cortisol levels are increased B. The adrenal gland is fully functioning C. Corticotropin releasing hormone is not being inhibited D. Corticotropin levels are decreased E. The patient will have hypertension
Question #8 Which of the diagnoses do you think best fits the patient’s symptoms?
A. Diuretic misuse B. MDMA use C. Primary Adrenal Insufficiency D. Secondary Adrenal Insufficiency E. None of the above
Question #8 Which of the diagnoses do you think best fits the patient’s symptoms?
A. Diuretic misuse B. MDMA use C. Primary Adrenal Insufficiency D. Secondary Adrenal Insufficiency E. None of the above
Why We Can Rule Out Other Diagnoses
Diuretic Misuse A diuretic would lead to loss of potassium and hydrogen, leading to hypokalemia
and alkalosis… in patient, mild hyperkalemia and acidosis are observed MDMA Use
No hypertension Drug screen was negative; patient denied using recreational drugs
Secondary Adrenal Insufficiency Corticotropin releasing hormone and adrenocorticotropin levels were high Tests were done that showed that hypothalamus and pituitary were responding
normally
Rare disorder Most common cause in high-income countries: autoimmune
adrenalitis Symptoms:
primary adrenal insufficiency) Eosinophilia
of excess pigment on skin Cortisol deficiency leads to loss
of negative feedback; thus, corticotropin levels are elevated, leading to high levels of melanin and pigmentation.
Eosinophilia High eosinophil levels
Despite lack of hyperpigmentation, physicians decided to test for Addison’s Disease. Measured cortisol levels Measured corticotropin baseline Cosyntropin stimulation assay
Cortisol Baseline
Cortisol levels found to be 7.2 ug/dL… this is a normal result; for Addison’s Disease, low cortisol expected. In presence of critical illness (such as patient) cortisol levels expected to
be high. So considering context, cortisol lower than expected.
Corticotropin Baseline
Found to be very high (896 pg/mL; baseline 6-76) Suggests Addison’s Disease
Question #9 How could you directly measure adrenal gland function?
A. Measure estrogen hormone levels B. Check salt concentration in urine C. Inject corticotropin and measure response D. Run an oxytocin activity assay E. A and D
Question #9 How could you directly measure adrenal gland function?
A. Measure estrogen hormone levels B. Check salt concentration in urine C. Inject corticotropin and measure response D. Run an oxytocin activity assay E. A and D
Cosyntropin Stimulation Assay
Cosyntropin is an active fragment of corticotropin
The idea is to inject cosyntropin intravenously and measure adrenal response Cosyntropin
Question #10 After injection of cosyntropin, cortisol levels are measured after 30 minutes and 60 minutes. If a patient’s adrenal glands are functioning normally, which of these test results are possible? (assume baseline cortisol level of 4.5 ug/dL)
A. 30 minutes: 6.7 ug/dL, 60 minutes: 8.9 ug/dL B. 30 minutes: 2.5 ug/dL, 60 minutes: 1.3 ug/dL C. 30 minutes: 10.7 ug/dL, 60 minutes: 10.8 ug/dL D. 30 minutes: 4.6 ug/dL, 60 minutes: 4.5 ug/dL E. A or C both indicate appropriate adrenal function
Question #10 After injection of cosyntropin, cortisol levels are measured after 30 minutes and 60 minutes. If a patient’s adrenal glands are functioning normally, which of these test results are possible? (assume baseline cortisol level of 4.5 ug/dL)
A. 30 minutes: 6.7 ug/dL, 60 minutes: 8.9 ug/dL B. 30 minutes: 2.5 ug/dL, 60 minutes: 1.3 ug/dL C. 30 minutes: 10.7 ug/dL, 60 minutes: 10.8 ug/dL D. 30 minutes: 4.6 ug/dL, 60 minutes: 4.5 ug/dL E. A or C both indicate appropriate adrenal function
Results of Patient’s Cosyntropin Assay? Her cortisol was 4.5 ug/dL before administration of test After 30 minutes, her cortisol level was 4.6 ug/dL; after 60 minutes, it was
4.5 ug/dL. With a functioning adrenal gland, cosyntropin injection should cause an
increase in cortisol The increased cortisol will later negatively feedback to inhibit corticotropin Patient showed no increase in cortisol levels in response to cosyntropin
injection.
Treatment
Treated by giving glucocorticoids (hydrocortisone) to replace adrenal gland cortisol output
Treated by giving mineralocorticoids (fludrocortisone) to replace adrenal gland aldosterone output
But there are still many problems with glucocorticoid and mineralocorticoid treatment due to: Varying glucocorticoid sensitivity from patient to patient It does not simulate normal pulsatile secretion of corticotropin and cortisol Exact amounts needed cannot be measured precisely
Management Dietary treatment; increase salt intake
This can cause other problems like hypertension and edema Avoid too much sun exposure
This can cause excess sodium and water loss Condition is chronic, not acute
After more probing history questions, it was discovered that she had been feeling fatigued for months. Hyperpigmentation was missed in initial assessment.
Autoimmune or another cause? Tested for 21-hydroxylase antibody, commonly seen in autoimmune
primary adrenal insufficiency Her results were negative, but that does not definitively rule out autoimmune
possibility… other antibodies may be involved for which tests are not available
Could do an abdominal CT to check for cancer, tuberculosis, granulomatous diseases, or other non-autoimmune causes Her physicians elected not to do that because there was not evidence to
suggest these diagnoses
Follow Up After discharge, patient was receiving 10 mg hydrocortisone at 8am and 5
mg at 3pm daily, along with 0.1 mg fludrocortisone. Fatigue in the morning→ attributed to taking the hydrocortisone too late in the morning Hands were puffy→ attributed to excessive fludrocortisone administration Bruising, muscle loss, 14 lb weight gain→ attributed to too large of a hydrocortisone
dose Medication was modified: 10 mg hydrocortisone at 7 am, followed by 2.5 mg
in the afternoon. Fludrocortisone was skipped twice a week. After another follow up three months later, symptoms had resolved and
patient was doing remarkably well.
Bonus Question
Which famous person was also diagnosed with Addison’s disease? A. Selena Gomez B. Meryl Streep C. David Bowie D. Martin Luther King Jr. E. John F. Kennedy
Bonus Question