1. Adrenal and Thyroid Diseases ( seen in acutely ill patients)
January, 2010
Deepika Reddy, md

2. Case 1
The patient is a 22 year with no prior medical history. About 6 weeks prior to coming to the ER she started to have palpitations, tremors and diarrhea. She also reports 25 lb weight loss over the past 2 months. She presented to the emergency room with, nausea/vomiting and abdominal pain.
She also complained of an inability to catch her breath
She vomited 10 times in 24 hours

3. Case 1
On physical exam, her temp was F. Her HR was 120. BP 130/90
She was thin, skin was warm to touch. Mild bilateral proptosis
Thyroid was diffusely enlarged, soft, no nodules
Heart: tachycardic but regular, no murmurs.
Lungs CTA, no crackles, no wheezes
Abdomen: minimal discomfort on abdomen palpation, not localized
Ext: mild edema, tremors of hands

4. Case 1 Labs’: TSH was undetectable FT4 : 7.72 (.76-1.46)
WBC 3.2, Hgb 11.4
LFTs normal

5. Signs and symptoms of Thyrotoxicosis
Neuropsychiatric/Neuromuscular Emotional lability
Anxiety
Confusion
Coma
Muscle wasting
Hyperreflexia
Fine tremor
Periodic paralysis
Gastrointestinal
Diarrhea
Reproductive Oligomenorrhea
Decreased libido
Gynecomastia
Spider angiomas
Thyroid gland Neck fullness
Tenderness
Diffuse enlargement
Bruit

6. Signs and symptoms of Thyrotoxicosis
Cardiorespiratory Palpitations
Dyspnea
Chest pain
Atrial fibrillation
Sinus tachycardia
Hyperdynamic precordium
Congestive heart failure
Dermatologic
Hair loss
Pretibial myxedema
Warm, moist skin
Palmar erythema
Ophthalmologic Diplopia
Eye irritation
Exophthalmos
Ophthalmoplegia
Conjunctival injection
NOTE: Elderly patients may not have the classic symptoms: Apathetic hyperthyroidism

7. Lab Findings in Thyrotoxicosis
Hyperglycemia (catecholamines reduce insulin secretion)
Hypercalcemia ( due to dehydration, increased bone resorption)
Increased LFTs
Increased alkaline phosphatase

8. Diagnostic Criteria for Thyroid Storm
Thermoregulatory dysfunction
Temperature
99–
100–
101–
102–
103– R
Central nervous system effects
Absent
Mild (agitation)
Moderate (delirium, psychosis, extreme lethargy 20
Severe (seizures, coma) 30
Gastrointestinal-hepatic dysfunction
Absent
Moderate (diarrhea, nausea/vomiting, abdominal pain) 10
Severe (unexplained jaundice) 20

9. Diagnostic Criteria for Thyroid Storm
Cardiovascular dysfunction
Tachycardia (beats/minute)
90–
110–
120– R
Congestive heart failure
Absent 0
Mild (pedal edema) 5
Moderate (bibasilar rales) 10
Severe (pulmonary edema) 15
Atrial fibrillation
Present 10
Precipitating event

10. Diagnostic Criteria for Thyroid Storm
Scoring system: A score of 45 or greater is highly suggestive of thyroid storm; a score of 25–44 is suggestive of impending storm, and a score below 25 is unlikely to represent thyroid storm.
Endocrinol Metab Clin N Am 35 (2006) 663–686

11. Management: General Plan
Stop synthesis of new hormone within the thyroid
gland (anti thyroid drug ATD)
Halt the release of stored thyroid hormone from the thyroid gland ( iodide such as SSKI)
Prevent conversion of T4 to T3 (ATD, beta blocker, steroids)
Control the adrenergic symptoms associated with thyrotoxicosis (beta blocker)
Control systemic decompensation with
supportive therapy (steroids, acetominophen)

12. Decreased Synthesis of Thyroid hormone: Anti thyroid Medication
WHICH ONE IS BETTER?
PTU
It is a Thiouracil: reduces synthesis of hormone and reduces T4 to T3 conversion
Short half life
Associated with hepatitis and increased risk of hepatic failure compared to methimazole . Onset of hepatic dysfunction variable and unpredictable
Also associated with agranulocytosis (0.37%) It is idiosyncratic and not dose related.
Can dose PO or rectally
In storm, start at mg q6 hrs.
The drug of choice in pregnancy.

13. Decreased Synthesis of Thyroid hormone: Anti thyroid Medication
Methimazole
Is an imidazole: decreases synthesis of thyroid hormone
Longer half life
Associated with hepatic dysfunction which is usually cholestatic. Onset is variable and unpredictable
Also see agranulocytosis (0.35%). It is dose dependent and rarely seen in doses less than 40 mg a day.
Can dose PO, rectally or IV
In storm can give 80 – 100 mg a day in divided doses.

14. Halt Release of Stored Hormone from the Thyroid: IODIDE
Can be given in the form of Super Saturated Potassium Iodide (SSKI) or Lugols Solution
Lugols 4-8 drops q6-8 hrs
SSKI 5 drops q6 hrs
HAS TO BE GIVEN AFTER THE ATD
Wait at least 1 hour
Max effect 7-14 days, if no other Rx given patients will get toxic again in this time frame.

15. Block Conversion from T4 to T3
ATD (PTU)
Beta Blockers
Glucocorticoids
Glucocorticoids also treat relative adrenal insufficiency
Typically hydrocortisone 100 mg q8hrs
If patient is elderly and worried about fluid retension may try Decadron 2 mg IV q6 hrs

16. Control Adrenergic Symptoms
Beta Blockers
Traditionally propranalol used.
Large doses may be required. Start at 40mg q8 hours titrate up to keep HR in 80’s
Can use Esmolol, atenolol, metoprolol as well

17. Other agents
LITHIUM can be used if ATD allergy is encountered and surgery not an option
It reduces formation and release of thyroid hormone
Dose in thyroid storm 300 mg q8 hrs
Need to check Lithium levels and keep level between 0.6 – 1.0
CHOLESTYRAMINE : Reduces Thyroid hormone absorption from gut.
It can affect absorption of other medications

18. Supportive Care
Avoid salicylates: they cause decreased binding of thyroid hormones to proteins.
In atrial fibrillation, may need warfarin. If already on warfarin, may need to reduce dose due to increased clearance of Vit k dependent clotting factors.

19. Case 1 continued
The patient was started on ATD, SSKI, beta blockers, steroids
On day 3, she was noted to have a significant drop in WBC count specifically a drop in granulocyte percentage.
Surgery was consulted since she was still symptomatic. She was taken to the OR and had a sub total thyroidectomy

20. Surgical Option When rapid control of thyrotoxicosis is required
When patients have allergies/side effects to ATD and need surgical intervention for thyrotoxicosis
Patients should be prepared with ATD ( if tolerated, iodide, steroids and beta blockers)

21. Case 2
The patient is a 33 year old African American patient with a past history of hypothyroidism presented with increasing lethargy and confusion reported by family. She had missed a clinic visit and did not get her thyroid medication refilled. She had been off levothyroxine for 4 months. She was seen about 5 months ago, at which point her TSH was 42, F T4 was .2
Now her TSH is 55 and FT4 is .23
She has had weight gain 37 lbs in six months, constipation, cold intolerance, amenorrhea for over a year. She recently had a URI. She has sleep apnea and was using her CPAP machine

22. Case 2 Physical BP 112/70, HR 64, Temp 96.5
Gen: Lethargic but arousable
HEENT: skin / hair dry, Periorbital edema, facial swelling. Significant swelling of the tongue, she did not completely close her mouth because of macroglossia
Lung: Good air movement in all lung fields
Heart: Slow normal in rate, regular
Abd: Obese, few BS, non tender
Ext: swelling of lower extremities
Neuro: drowsy but arousable, answering questions appropriately.

23. Labs ABG showed hypoxia and hypercapnea
Chemistry panel showed low glucose of 67 and
Sodium was 129

24. Clinical Features of Myxedema
Lethargy and confusion
Hypothermia
Bradycardia
Reduced cardiac contractility
Hypotension
Hypoxia/ hypercapnia due to reduced respiratory drive
Nausea/abdominal pain/reduced gastric motility
Electrolyte abnormalities : hyponatremia, Hyperkalemia

25. Management Mortality rates high Should be in ICU setting
Assess airway , May need mechanical ventilation.
Dextrose and fluid resuscitation since may be hypovolemic
Steroids should be considered especially if hypotensive
May need hypertonic saline and lasix if hyponatremia severe
Hypothermia should be corrected carefully since it may result in hypotension.
Also evaluate carefully for precipitating event such as infection/ischemia

26. Management Thyroid hormone replacement critical.
Some controversy over the way in which to replace the thyroid hormone
Some recommend large loading dose of T mcg IV followed by mcg daily IV
Use lower doses in the elderly with cardiovascular disease
Some suggest that the T4 to T3 conversion is impaired in the severely ill. They suggest T3 IV upto 20 mcg, the q6 hrs

27. Management
Can switch to PO levothyroxine after the patient has a bowel movement.
Extubate only when patient has shown significant improvement. Wait till patient regains conciousness.
Monitor closely till vitals, cardio-respiratory status, neurologic and GI symptoms improve.

28. Case 2 Our patient was watched in the progressive care unit
On Bipap for her respiratory difficulties
Given ‘loading dose’ of 200 mcg of Levothyroxine IV. Then 100 mcg a day IV till she had a bowel movement then switched to a weight based dose ( 1.5 x weight in KG) Received dextrose, IVF.
Clinically improved over the next 3-4 days

29. Case 3
A 78 year old gentleman presented to the ER with N/V , loose stool, confusion over 24 hrs. In ER noted to have hypotension 70/50.
Relevant past history: Has had a GH secreting pituitary macroadenoma resected 30 years earlier. He was on Pred 5 mg a day. He had recent ( 2 weeks ago ) been to the dentist who noted he had an oral infection and given him and antibiotic. About 2 days prior to admission he started to have loose stool and over 24 hr had the rest of symptoms develop. He had not changed his does of steroid during this time
Labs: mild hypoglycemia, hyponatremia and elevated WBC count.

30. Case 3 PE: BP 78/60, HR 115 Temp 101.3 sats OK
Gen : Confused, not oriented. Unable to get any history.
HEENT: pupils were reactive to light
Lungs: good air movement and clear to ausculatation
Cardiac : tachycardic no murmurs
Abd : distended, tender, mostly lower quadrants
Skin: dry, no hyperpigmentation
Rest of exam unremarkable.

31. Who presents in adrenal crisis?
Patients with undiagnosed chronic adrenal insufficiency who have a ‘stressful event’ such as an infection. Or recent event such as bilateral adrenal hemorrhage
Patients with known primary adrenal insuffieciency who did not received adequate glucocorticoid replacement. Like this patient.
There are instances where patients with secondary adrenal insufficiency present in crisis such and pituitary infarction.

32. Presenting features of adrenal crisis
Shock
Abdominal tenderness, N/V
Psychiatric manifestations: confusion, delirium, stupor
Fever
Hyperpigmentation, vitiligo,
Evidence of androgen deficiency in women with primary Adrenal insufficiency
Hypoglycemia ( more common in secondary adrenal insufficiency)
Electrolyte abnormalities
Primary low NA and high K
Secondary may have low Na due to vasopressin excess but K is usually normal

33. Evaluation of adrenal function in a patient with hypotension
Evaluation of adrenal function (which test to use)
Does the patient have primary or secondary adrenal insufficiency?
Evaluation of etiology if diagnosis has been confirmed
Are there other medical issues that need to be treated
Long term management of adrenal insufficiency
Interpretation of the test (does the test work as well in acutely ill patients?)

34. Evaluation Before Evaluation, ensure patient is stable
If a patient is in shock treat with steroid early
Use Decadron since it does not interfere with the testing
Hydrocortisone interacts with cortisol assay and therefore should be avoided prior to testing

35. Evaluation: ACTH Stim Test( Make sure this is done right!!)
Draw baseline ACTH and cortisol. Note the ACTH should be in a EDTA tube and kept on ice!
Then give Cosyntropin 250 mcg IV over 1 min
Draw cortisol 30 min and 60 min later
Interpretation: cortisol level of at least at either min indicates normal study
Note if the patient has been given ANY steroid this will affect ACTH levels

36. Assess level of defect/Etiology
The ACTH level ( if done before any steroids are given) can help separate primary from secondary adrenal insufficiency.
In adrenal crises, treat first if testing non – diagnostic or equivocal. Can figure out level of defect once patient is stable
Look for clues :
History of head trauma/radiation
post partum : severe headache, hypotension: think sheehans
On anicoagulation: ? Bilateral adrenal hemorrage
Infections: such as HIV may have primary adrenal insufficiency
Evidence of other pituitary hormone deficiency can be done when patient is stable.
In our patient: insufficient steroid when ill

37. Management
1)Treat with IV glucocorticoid Decadrone 2-4 mg IV before the study, Hydrocortisone after the study 100 mg IV q8hrs
2) Continue with IVF
3) Look for etiology and treat as needed

38. Case 3
Rapid improvement in mental status and cardiovascular complaints after steroids were given.
He was diagnosed with toxic megacolon due to clostriduim difficile.
Was advised on increasing steroid doses when ill
2-3 times normal daily dose. Decaron emergency Kit if he has N/V. ER if unable to control any other way.

39. Special considerations in acutely ill patients (patients in septic shock)
A systemic review (Annane et al JAMA 2009, 301 (22) ) demonstrated that glucocorticoids do not affect 28 day mortality in patient with sepsis (including those in shock)
A sub group analysis showed that low dose, longer duration of glucocorticoids may have mortality benefit

40. Special considerations in acutely ill patients
The ACTH stimulation test may not reflect adrenal function in acutely ill patients since hypoproteinemia can affect total cortisol levels.
Current recommendations suggest that low dose glucocortcoids may be considered in patients with hypotension, on fluids and vasopressors who do not respond to these measures