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

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

Case 1 On physical exam, her temp was 101.5 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

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

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

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

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

Diagnostic Criteria for Thyroid Storm Thermoregulatory dysfunction Temperature 99–99.9 5 100–100.9 10 101–101.9 15 102–102.9 20 103–103.9 25 R104.0 30 Central nervous system effects Absent 0 Mild (agitation) 10 Moderate (delirium, psychosis, extreme lethargy 20 Severe (seizures, coma) 30 Gastrointestinal-hepatic dysfunction Absent 0 Moderate (diarrhea, nausea/vomiting, abdominal pain) 10 Severe (unexplained jaundice) 20

Diagnostic Criteria for Thyroid Storm Cardiovascular dysfunction Tachycardia (beats/minute) 90–109 5 110–119 10 120–129 15 R140 25 Congestive heart failure Absent 0 Mild (pedal edema) 5 Moderate (bibasilar rales) 10 Severe (pulmonary edema) 15 Atrial fibrillation Present 10 Precipitating event

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

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)

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 200-300mg q6 hrs. The drug of choice in pregnancy.

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.

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.

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

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

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

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.

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

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)

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

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.

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

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

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

Management Thyroid hormone replacement critical. Some controversy over the way in which to replace the thyroid hormone Some recommend large loading dose of T4 300-500 mcg IV followed by 50-100mcg 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 2.5 -5 q6 hrs

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.

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

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.

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.

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.

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

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?)

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

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 18-20 at either 30-60 min indicates normal study Note if the patient has been given ANY steroid this will affect ACTH levels

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

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

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.

Special considerations in acutely ill patients (patients in septic shock) A systemic review (Annane et al JAMA 2009, 301 (22) 2362-2375) 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

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