A 59 year old male presented with three months of nausea, altered mental status, difficulty urinating

LEARNING OBJECTIVES:  1. Recognize the symptoms and signs that suggest secondary hypertension 2. Diagnose adrenal adenoma using clinical and radiographic criteria

CASE:  A 31-year-old man presented with five days of shortness of breath. His baseline dyspnea on exertion increased from shortness of breath at five blocks, to walking 30 feet. His one-pillow orthopnea increased to sleeping for minutes at a time sitting straight up in bed; he developed new onset paroxysmal nocturnal dyspnea and pedal edema. The shortness of breath was associated with a cough productive of clear sputum and fatigue. He has a past history of hypertension and systolic dysfunction. His out-patient medications included clonidine, metoprolol, and K-dur 40 meq. His blood pressure was 195/126 mmHg, pulse 80 beats/min, respiratory rate 26 breaths/min, and temperature 38.3°C. He had eight cm of JVD, an S3 gallop, and bibasilar crackles. Despite his supplementation, his potassium was 2.7 mg/L. He had LVH on EKG and bilateral cephalization on chest X-ray. He was admitted with the diagnosis of a CHF exacerbation and treated with diuresis and blood pressure control. The inability to control his blood pressure despite several medications and the continuing potassium supplementation requirements in the absence of a diuretic prompted an evaluation for the diagnosis of primary hyperaldosteronism. This was confirmed with a serum aldosterone of 21.3 (normal <16) and a rennin level of <0.8. An abdominal/pelvic CT showed an 18 × 14 mm round adrenal mass with central attenuation.

DISCUSSION:  Primary hypertension is so common as to mask the red flags of secondary hypertension. A search for secondary causes of hypertension should be initiated when faced with any of the following: hypertension in youth, hypertension requiring multiple medications, episodes of flash pulmonary edema or unexplained congestive heart failure, hypertension with unexplained electrolyte abnormalities, and any of the above coupled with an incidentaloma found on CT. The patient in this case presented was diagnosed with hypertension at the age of 26, and his blood pressure was poorly controlled while being treated with multiple medications. He required potassium supplementation despite not being on potassium-wasting medications. He was hospitalized twice for unexplained congestive heart failure and had a benign adenoma was discovered on abdominal CT. Following the removal of his adrenal adenoma, his hypertension resolved.

LEARNING OBJECTIVES:  LEARNING OBJECTIVES: 1) Correctly interpret thyroid function tests (TFTs) in pregnancy 2) Review the relevant differential diagnosis and management of hyperthyroidism in the pregnant patient.

CASE:  We were asked to consult on a 22-year-old woman at 18 weeks gestation for elevated blood pressure and abnormal TSH. She had been healthy until 3 months prior to presentation when she first noted increasing lower extremity edema. She had also noted blurry vision and headache in the preceding week. In the emergency room, she was noted to be tachycardic (102/min) and hypertensive (190/110 mmhg). Her physical exam was unremarkable except for a fine tremor of the hands and 3+ pitting pedal edema. A urine dipstick revealed 3+ proteinuria. Lab abnormalities were consistent with preeclampsia. A TSH level was found to be <.01 U/ml. Her full thyroid function panel was consistent with hyperthyroidism. She was admitted with a diagnosis of thyrotoxicosis and severe preeclampsia at early gestational age. A fetal ultrasound revealed multiple congenital anomalies consistent with triploidy. The patient chose to terminate the pregnancy. Placental pathology was consis-tent with a partial hydatiform mole. Postpartum, the patient’s tachycardia, hypertension and tremor resolved within a day. A -hCG level on the third postpartum day was still elevated at 42,700 u/ml. At her 6-week postpartum check, the patient was well, with normal thyroid function tests and -hCG level <5 u/ml.

DISCUSSION:  Hyperthyroidism is the second most common endocrine problem encountered in pregnant women. Recent evidence has emphasized the importance of a euthyroid state in pregnancy for favorable maternal and fetal outcomes. Internists should be prepared to diagnose and manage thyroid disease in pregnancy. Changes in serum concentrations of thyroid hormones and thyroxine-binding globulin during pregnancy make the interpretation of TFTs in pregnancy difficult. The expected changes in TFTs with each trimester and their relationship to hCG levels will be dis-cussed. The pathophysiology, clinical presentation and management of hyperthyroidism in pregnancy will be discussed. Typical causes of hyperthyroidism in pregnancy, including Grave’s disease and Hashimoto’s thyroiditis will be reviewed and differentiated from hyperthyroidism associated with gestational trophoblastic disease and hyperemesis gravidarum.

LEARNING OBJECTIVES:  1. To enhance clinician awareness of the need for HIV testing in the elderly. 2. To recognize the importance of a complete history. 3. To recognize the need for further research on HIV prevention and treatment among the elderly.

CASE:  A 77 year old Cape Verdean-male was admitted with trigeminal zoster. Past medical history was significant for hypertension, pneumonia with sepsis, recurrent urinary tract infections, anemia of chronic disease, malnutrition, ischemic cardiomyopathy, and renal insufficiency. He was a nonsmoker and denied IVDU or prior transfusions. His wife had recently died of unknown causes. Three years prior to admission, a persistently elevated total protein prompted an evaluation for multiple myeloma. Bone marrow biopsy revealed a polyclonal gammopathy and a skeletal survey was negative. Subsequently a leukemia and lymphoma panel was unremarkable. Prior to admission he was being followed by a hematologist for Monoclonal Gammopathy of Undetermined Significance. As an inpatient with trigeminal zoster he tested positive for HIV with a CD4 count of 70 and a viral load of 38,386, suggesting advanced disease. HAART therapy was instituted after discharge with suppression of his viral load. He died of an arrhythmia almost 2 years later in the setting of decompensated heart failure.

DISCUSSION:  Individuals over 50 years of age account for up to 10% of AIDS cases reported to the CDC, a number that is expected to rise as a result of improved survival of patients with treated disease. Older adults are less likely to use a condom during sexual intercourse or to participate in HIV testing. Older adults with HIV infection are more likely to be diagnosed late in disease due to delayed recognition, they experience progression more quickly, and they survive for shorter periods of time than their younger counterparts. Co-morbidities often complicate management and controlled data on tolerability and responses to HAART are lacking. The possibility of HIV infection must be considered among elderly patients with clinical features of immunodeficiency in order to avoid delay in counseling and treatment. This case emphasizes the importance of conducting the sexual history, regardless of age, and it underscores the need for age-appropriate prevention and treatment strategies.

LEARNING OBJECTIVES:  1. Recognize the complications of jejeunoileal bypass prior to the onset of liver failure 2. Recognize the presentation of vitamin deficiency.

CASE:  A 62 year-old white woman presented with a two-year history of intermittent jaundice and a three-week history of increasing abdominal girth. She had a history of jejeunoileal bypass in 1978 for morbid obesity. She had been admitted fourteen months prior with a hemoglobin of 4 g/dl, an elevated bilirubin, and a prolonged prothrombin time. She was diagnosed with B12 deficiency and malabsorption of fat soluble vitamins. A CT at that time showed diffuse fatty infiltration of the liver. On exam she had peripheral wasting, spider angiomas, shifting dullness, jaundice, and peripheral edema. On admission, she had a prolonged prothrombin time, a normal hemoglobin, an elevated bilirubin, and low cholesterol levels. An abdominal CT revealed large volume ascites and a cirrhotic liver. Paracentesis was consistent with portal hypertension as an etiology for the ascitic fluid. A liver biopsy showed severe steatosis with cirrhosis.

DISCUSSION:  Jejeunoileal bypass has been a common treatment for morbid obesity, but has rapidly lost favor due to its severe long term consequences, including arthritis, B12 deficiency, cirrhosis, and chronic diarrhea. Patients who received this procedure are now coming to the attention of physicians because of cirrhosis. Unfortunately, this patient was regularly followed in the medicine clinic but did not undergo hepatic evaluation because her symptoms were attributed to the altered physiology of bypass. The intermittent episodes of jaundice following the correction of the B12 deficiency suggested another underlying pathology. Similarly, the prolongation in the prothrombin time following replacement of vitamin K should have been a clue that there was impaired hepatic synthetic function. The CT scan of the abdomen was also potentially confusing: because of the morbid obesity, hepatic steatosis was attributed to NASH. Prompt recognition of this complication of jejeunoileal bypass is important to refer patients to a hepatologist to prevent the expected fifty percent mortality after the development of ascites. At present our patient is awaiting liver transplant.

LEARNING OBJECTIVES:  1. To recognize Creutzfeldt-Jakob Disease (CJD) as a cause of tremor and myoclonus. 2. To appreciate the value of performing a brain biopsy to confirm a diagnosis of CJD.

CASE:  A 70 year-old female presented with a 6-week history of abnormal motor movements. Initially, she developed an action tremor in the right arm. After 4 weeks, the left arm also became affected and she began to experience myoclonus in both arms. On physical exam, the patient appeared well-nourished and was afebrile. Her Mini-Mental Status Exam score was 30/30. CNs II-XII were intact. Action-induced myoclonic jerks were noted in both arms (R > L). Strength was 5/5 in all extremities. Sensory testing was normal. DTR’s were +2 and symmetric. Romberg test was negative. Cerebellar testing was normal. A brain MRI was performed revealing “gyriform” signal changes in the parietal-occipital region bilaterally. This raised suspicion for a diagnosis of encephalitis. As a result, a lumbar puncture was performed that showed no evidence of pleocytosis or increased protein. Over the next 4 weeks, the patient developed worsening neurological changes, including: dysarthria, ataxia, and increased myoclonus. A repeat brain MRI was unchanged. An EEG was normal. Serological studies looking for evidence of an autoimmune disease were negative. Anti-Hu and anti-Yo antibodies were negative. Since a diagnosis remained elusive and the patient’s clinical condition continued to deteriorate, a brain biopsy was performed. The pathology revealed spongiform changes consistent with CJD. The patient’s neurological impairment progressed, including the development of dementia, and she died 2 weeks later.

DISCUSSION:  CJD is a degenerative disease of the central nervous system that is caused by infectious proteins called prions. Various forms of CJD have been recognized including: sporadic, familial, iatrogenic, and new-variant CJD. Most patients with CJD have the sporadic form and present with some degree of cognitive impairment and tend to progress rapidly to a state of dementia. A myriad of other neurological signs and symptoms may develop throughout the course of the illness with >90% of patients developing myoclonus. A typical clinical course may suggest CJD, but confirming this diagnosis can be challenging. Blood and CSF analyses can help exclude other conditions that may mimic CJD. Most patients demonstrate characteristic periodic complexes on EEG and/or abnormal signal patterns on MRI, but these findings are nonspecific. The gold standard for diagnosis remains brain biopsy. This case is unique in that cognitive impairment did not develop until extremely late in the course of the illness. It also emphasizes how an atypical clinical presentation, the absence of the more common EEG and/or MRI abnormalities, and a lack of risk factors for prion disease, can result in the delay of a diagnosis of CJD being made.

LEARNING OBJECTIVES:  1. Recognize the common and uncommon abnormal laboratory findings associated with sickle cell disease. 2. Recognize hepatitis as a complication of vaso-occlusive crisis.

CASE:  A 36 year-old woman presented with one week of worsening pain in her back, lower extremities, and nauseaand vomiting. She had a history of sickle cell anemia and a recent pulmonary embolism Her vital signs were normal; she had hepatomegaly and tenderness in the right upper quadrant. There was also pain in her back and lower extremities. Her alkaline phosphatase was 71, total bilirubin 1.3, AST 1968, and ALT 2088. Her viral hepatitis panel was negative; she denied alcohol use. Her acetaminophen and salicylate were normal. She was treated for five days with intravenous fluids and pain medication, and her liver enzymes decreased with resolution of her abdominal pain. She returned ten days later; her has AST (53) and ALT (67) has both decreased.

DISCUSSION:  Sickle cell disease is characterized by arterial occlusions due to micro-thrombi from the sickled cells. Peripheral vaso-occlusion is the most common since systemic vascular resistance is higher in these vessels and they are of smaller caliber. The result is the typical bone and muscle pain of a sickle cell crisis. Solid organs can also be involved, however, resulting in myocardial infarction, stroke, renal impairment and, in this case, ischemic hepatitis. Although ischemic hepatitis is seen in only ten percent of all sickle patients, physicians should be vigilant for the complication, especially in the setting of right upper quadrant pain, hepatomegaly, jaundice, and a low grade fever. The usual laboratory findings are elevated AST and ALT levels. Treatment is supportive care with IVF and pain control; hepatitis that does not resolve warrants exchange transfusions.

LEARNING OBJECTIVES:  1. Diagnose Multicentric Castleman’s Disease. 2. Recognize the association between Castleman’s Disease, HHV-8, and HIV.

CASE:  The patient is a 39 year-old HIV+ man (CD4 23) who presents with worsening fevers and increasing abdominal pain for 1 week. He reports onset of intermittent fevers 18 months ago; 1 week ago, the fevers began to occur daily, accompanied by abdominal pain, headaches, back pain, and nausea. The patient recalled a similar symptom constellation 7 months before that resolved spontaneously. He has Karposi’s Sarcoma (KS) and takes abacavir/3TC/AZT, lopinavir, tenofovir, azithromycin, and TMP/SMX. On admission the patient was afebrile with normal vital signs. His exam was remarkable for axillary and inguinal lymphadenopathy (LAD); a soft abdomen, mildly tender to palpation diffusely; KS lesions on the left lower extremity. Laboratory studies showed anemia but were otherwise normal. While hospitalized the patient spiked daily fevers, unrelated to antiretroviral administration. Blood, urine, CSF and MAC cultures all were negative, as were an influenza panel, monospot test, and cryptococcus serology. Chest radiography and head CT were normal. Abdominal CT revealed splenomegaly and diffuse LAD. Biopsy of an axillary lymph node showed Castleman’s disease (CD) and stained positive for human herpes virus 8 (HHV-8).

DISCUSSION:  The differential diagnosis for fever and LAD, already extensive, is even broader in patients with advanced HIV. In this case, the leading diagnoses included disseminated TB, MAC, and non-Hodgkin’s lymphoma. CD, which also manifests with fever and LAD, is a rare lymphoproliferative disorder which has received renewed interest as increasing case reports link it to HIV and HHV-8. The unicentric form of CD is isolated, usually asymptomatic, and often discovered incidentally. Not typically associated with HHV-8, it can be cured with surgical resection. Multicentric CD (MCD), as seen in this patient, has systemic symptoms. Effective therapeutic options are limited, contributing to a poor prognosis. The disease manifests differently in patients with and without HIV and HHV-8. HIV+ patients with MCD are universally positive for HHV-8, and are more likely to have a rapidly progressive course with a shorter survival. New studies suggest that HHV-8 may contribute more to this pattern than HIV. Patients typically die of fulminant infection or associated malignancies. Optimal treatment is unclear given the rarity of the disease, the variety of clinical presentation, and the paucity of literature. Most therapies offer a temporary response with relapse after discontinuation, but combination chemotherapy and rituximab show promise for more durable responses. Castleman’s disease is a rare disorder with a clinical course shaped by the presence of HIV and HHV-8; it should considered in any HIV+ patient with KS, fevers, and lymphadenopathy.

LEARNING OBJECTIVES:  1. Recognize that viral infections are a common cause of rhabdomyolysis. 2. Recognize that a muscle biopsy is the gold standard for diagnosis of rhabdomyolysis. 3. Realize that congenital diseases can have initial presentation in adulthood.