COMBINED ADRENAL CRISIS AND MYXEDEMA COMA DUE TO HYPOTHYROIDISM. K. Kamjoo 1 , N. Michail 2 ; 1 University of California, Los Angeles, Sherman Oaks, Ca; 2 UCLA LEARNING OBJECTIVES: 1-To recognize the clinical presentation of severe hypopituitarism. 2-To understand the physiology of pituitary hormones. 3-Patient compliance as a cause of serious illness. CASE INFORMATION: A 37 years old female with a history of pituitary adenoma status post trans-sphenoid resection in 1990, was brought to Emergency Department (ED). Pt was not responsive and paramedics' report indicated that patient had gotten worse over the past month with progressive lethargy, vomiting, and altered mental status. Patient had stopped her medications approximately one year prior to admission. In ED patient was comatose and her initial vitals were: Rectal temperature 33.3 C, pulse 64, respiration rate 14, blood pressure 80/ 44, and blood sugar of 26. On physical exam patient appeared pale and had marked facial puffiness. She had no heart murmur but was bradycardiac. Patient's neuro exam showed bilateral hyperreflexia with a definite delay in the relaxation phase of her deep tendon reflexes. Patient's skin was very dry and she had no axillary or pubic hair. CXR only showed mild cardiomegaly. EKG showed sinus bradycardia with diffuse low voltage and flat T-waves. Patient was given 2L of intravenous (IV) D5W and 100 mg of IV hydrocortisone. After administration of IV steroids, patient's core temperature increased to 37.2 C and her blood pressure was stable at 89/50. She had an O2 saturation of 100% on room air and became conscious and alert. Subsequently, she was admitted to step-down unit with a diagnosis of adrenal crisis due to untreated hypopituitarism. Patient was started on DDAVP, and hydrocortisone. Serum TSH and free T4 were pending at this time and patient was started on 0.1 mg of oral Synthroid. Patient was doing well after the first day of hospitalization. However, on the second day her mental status deteriorated again and became obtunded. She had increased puffiness in her face and marked edema of her lower and upper extremities. Patient's blood gas showed CO2 retention. Patient was diagnosed with myxedema coma and tranferred to medical ICU. Patient was intubated and a single 300 mcg dose of IV Levothyroxine was administered, followed by 100 mcg of IV Levothyroxine daily. At this time serum TSH and free T4 drawn on admission showed TSH = 0.1 and free T4 < 0.40. The patient subsequently improved markedly and was discharged from hospital after 7 days. DISCUSSION: Myxedema coma is a very rare disease occuring primarily in elderly patients with primary thyroid failure. This case illustrates the importance of early recognition that myxedema coma can occur in combination with adrenal crisis in patients with decompensated hypopituitarism. Non-compliance in this disease could lead to fatal consequences. A 56 year old male presented for routine primary care evaluation. His past medical history was significant only for mild COPD and tobacco use. He specifically denied any history of coronary artery disease,diabetes,hypertension or dyslipidemia. Review of systems identified long standing complaints of erectile dysfunction and fatigue. Specifically, the patient noted a frequent inability to reach orgasm and lower extremity fatigue when climbing stairs. Physical examination was notable for a blood pressure of 110/65,an arm span greater than height,intact lower extremity pulses,sparse male pattern hair distribution,gynecomastia,small penis size and small,firm testes. Pulse volume recordings of the lower extremities and electrocardiogram were unremarkable. Laboratory evaluation found LDL=68, fasting glucose=104,Hct=48,TSH=1.08,free testoster-one=2.6,LH=14,FSH=26 and prolactin=3.5. Subsequent chromosomal karyotyping indicated the presence of an 82% XXY pattern consistent with Klinefelter Syndrome. The patient was treated with intramuscular testosterone. On follow-up, this patient reported improved energy levels and sexual performance. Indeed, the patient presented with new complaints consistent with bilateral epicondylitis. Apparently, following diagnosis and therapy, this patient was now hard at work buffing combines! DISCUSSION: Klinefelter syndrome,a primary form of testicular failure, is a common disorder that affects 1 in 500 male patients. It results from nondisjunction during parental gametogenesis and yields an individual with an XXY karyotype. Individuals with Klinefelter syndrome do not progress through puberty and ultimately develop the clinical features of eunuchoidism. These features of androgen deficiency include:arm span greater than height,long legs,sparse male pattern hair distribution,gynecomastia,small testes and penis and infertility. Endocrine evaluation of patients with this syndrome indicates low free testosterone together with elevated gonadotropin levels (ie LH and FSH). Klinfelter syndrome is treated with testosterone supplementation. This produces positive changes in mood,behavior,muscle mass and bone density. Once testosterone supplementation is begun, patients must be routinely screened for erythrocytosis and lipid abnormalities. year-old man with history of recurrent spontaneous pneumothorax (he underwent pleurodesis 5 years ago), presented to our service complaining of 2 months of progressive abdominal swelling, leg edema, jaundice, and worsening shortness of breath. The patient is a chronic smoker who rarely consumes alcohol. On exam the patient was afebrile with a regular pulse of 110, blood pressure of 118/78, respiratory rate of 18/min, distended neck veins, S4 gallop, massive ascites and +3 leg edema. Other than high total/direct bilirubin 2.2/3.6, the labs were unremarkable. Echocardiogram revealed a markedly dilated right ventricle with moderate pulmonary hypertension, severe tricuspid regurgitation and left ventricle of normal size and function. Spiral chest CT revealed pulmonary embolism of both left lower and upper divisions of the pulmonary artery. Doppler ultrasound of both legs was negative. The patient was anticoagulated (heparin, then warfarin) and once stable discharged home. DISCUSSION: CTEPH results from single or recurrent pulmonary emboli arising from sites of venous thrombosis. Most emboli completely resolve spontaneously, or they have minimal residual effects. In CTEPH, for unclear reasons, the emboli do not resolve completely. Rather, the emboli undergo abnormal organization and recanalization, leaving endothelium-covered residua that obstruct or significantly narrow major branches of the pulmonary artery. This is very different from primary pulmonary hypertension, where obstructive lesions appear in the small distal pulmonary arteries. Most patients with CTEPH have history of venous thrombosis with embolism; however this history may not be elicited unless actively sought for. After the initial embolic event the patients' condition gradually improves and they usually resume their normal activities. This period of improvement is however a temporary``honeymoon period' frequently followed by more subclinical thromboembolic events. Recurrent pulmonary embolism destroys the pulmonary vascular bed and causes pulmonary hypertension. With time patients deteriorate and become dyspneic at lower levels of exertion. Clinically, they present with a triad of dyspnea, syncope and right heart failure. Initial treatment includes chronic anticoagulation; consider embolectomy for massive embolism. and thrombotic and vasculitis work up. Transesophageal echocardiography (TEE) with agitated saline demonstrated a PFO, with significant right to left shunt, with transcranial Doppler demonstrating contrast reaching cerebral circulation. The patient underwent surgical closure of PFO by direct suturing. The patient now presented with the fourth episode of transient right-sided numbness and paresthesia in the last three years. TEE with agitated saline showed no residual shunt. Patient was anticoagulated (heparin, then warfarin) and once stable sent home. DISCUSSION: Stroke causes more than 100,000 deaths in USA each year, and leaves many others with major disabilities. In 25 to 40% of strokes in young adults, an extensive evaluation fails to identify the cause; these are classified as crypotogenic strokes. Notably, patients with crypotogenic strokes have a higher incidence of PFO than patients with stroke of determined cause, even after correcting for presence of recognized stroke risk factors. Potential mechanism for PFO related ischemic event includes paradoxical embolism in which a thrombus dislodges from a venous thrombotic site, traverses the interatrial septum and reaches the brain. Other mechanisms may include a thrombus formation secondary to atrial arrhythmias or atrial septal aneurysm. The incidence of stroke will be higher as the size of a PFO increases and if it is associated with an atrial septal aneurysm. Treatment options for PFO may range from no therapy, to medical therapy, to surgical closure of PFO. Choosing the type of treatment would depend on the patient's age, surgical and anticoagulation risks. The average annual risk of recurrence of cardiovascular events is 3.8% for medical therapy (aspirin 250 ± 500 mg/d, warfarin with target INR 2 ± 3, or both together) and 2.5 % after percutaneus transcatheter closure of the PFO. Closure done through open heart surgery by direct suture or patch closure is the gold standard of therapy and offers permanent closure of the defect with minimal risk and avoidance of long term anticoagulation. Recurrence of cerebrovascular ischemic events is still possible after successful surgery. Having multiple neurological events before surgery is the only significant risk factor of recurrence after the procedure. One should try to identify causes other than paradoxical embolism in patients who experience recurrent cerebrovascular events after surgical closure of PFO.