A 56-YEAR OLD MALE WITH HEADACHES AND VOMITING
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1 A 56-YEAR OLD MALE WITH HEADACHES AND VOMITING
2 HISTORY OF THE PRESENT ILLNESS 56-year old male, with complicated medical history, including extensive cardiac disease and chronic kidney disease, presenting with: One month history of low grade, tension-type headache; acute worsening with sudden-onset smashing right-sided temporal headache on the night prior to admission. Headaches associated with nausea and recurrent emesis. No relief with Tylenol #3 or NSAIDS. No precipitating trauma. No associated vision changes, confusion, lethargy, rhinorrhea, or aura.
3 PAST MEDICAL & SURGICAL HISTORY Non-Ischemic Dilated Cardiomyopathy Orthotopic Heart Transplant 2005, complicated by cardiac allograft vasculopathy Re-transplant March 2013; s/p biv-aicd Mycophenolate mofetil Tacrolimus Predisone 5 mg Chronic Kidney Disease LECT-2 amyloidosis Hypertension Diet-controlled after transplant Dyslipidemia Pravastatin Barrett s Esophagus Esomeprazole Anemia Erythropoietin Cyanocobalamin Folate Ferrous sulfate Depression Citalopram
4 SOCIAL AND FAMILY HISTORY Lives between US and Mexico US Citizen since 2007 Lives with wife Quit tobacco in 2004 No etoh or illicit drug use Father died in 70s; Cause unknown Mother alive, healthy, in late 80 s 4 brothers, 4 sisters. 1 brother with heart failure, CVA 4 grown children (all with advanced professional degrees) living in Mexico
5 REVIEW OF SYSTEMS Constitutional: Denies fevers, chills, hot or cold intolerance. Reports fatigue, 20 pound weight loss (since transplant 6 mos. ago). HEENT: Denies vision changes including blurriness, loss of peripheral vision or double vision, tinnitus, rhinorrhea, trouble swallowing, neck pain or goiter. Worsening headaches, right molar dental caries worsening headache. Cardiovascular: Denies chest pain, palpitations or racing heart, syncope, lower extremity edema Respiratory: Denies difficulty breathing or shortness of breath, cough, or wheezing. Gastrointestinal: Denies changes in appetite, abdominal pain. Nausea, vomiting, and constipation. Genitourinary: Denies urinary symptoms. No erectile dysfunction or change in libido. Musculoskeletal: Diffuse arthralgias and occasional joint swelling in his arms. No changes in shoe, ring finger size. Neurological: Denies tremors, numbness, tingling, weakness. Skin: Denies diaphoresis, new rash, changes in hair or nails. New frontal acne. Psychiatric/Behavioral: Reports depressed mood, anxiety. Wife reports has been more nervous.
6 PHYSICAL EXAMINATION BP 129/83 P 92 T 36.6 R 81 O2 96% RA Wt 77.5 kg Ht cm GENERAL: Oriented to person, place, and time. Well-developed, well-nourished. No acute distress. Tired appearing. HEENT: EOMI. Oropharynx clear. No frontal bossing or macroglossia is evident. There are no gross visual field deficits to confrontation. NECK: Supple. Thyroid soft. There is no apparent goiter or thyromegaly. No acanthosis nigricans or skin tags are noted. CV: Regular rate and rhythm. No murmurs, rubs, or gallops are appreciated. No JVD. RESP: Good respiratory effort, clear to auscultation bilaterally with no wheezes or rales. ABD: Soft, non-tender, non-distended. Normal bowel sounds present. No hepatosplenomegaly is appreciated. There are no violacieous striae. GENITOURINARY: No galactorrhea expressed from nipples bilaterally. MSK: Normal range of motion. No edema. 2+ distal peripheral pulses. NEURO: No tremors. Normal gait. Normal reflexes with no change in relaxation phase. SKIN: Skin is warm and dry. Frontal acne is present. PSYCH: Normal mood and affect. Behavior, thought content appear normal.
7 DIAGNOSTIC EVALUATION Glucose 105 Sodium 140 Potassium 4.2 Chloride 101 CO2 23 Anion Gap 16 BUN 50 Creatinine 2.3 WBC 6.3 HGB 14.2 HCT 43.2 PLT 180 CSF Analysis Total cell count 25 RBC 25 Glucose 75 Protein 44 Bacterial, Fungal, HSV, CMV, JCV, Cryptococcal, AFB cultures Negative GFR 30 Calcium 10.0 Albumin 4.1 Total Protein 6.1 TSH 1.37 T bili 0.5 Alk Phos 29 AST 21 ALT 11
8 DIAGNOSTIC EVALUATION OF HEADACHES - CT HEAD WO Soft tissue density is demonstrated extending from the left cavernous sinus region into the left sella turcica. Ddx includes tortuous cavernous portion of internal carotid artery, meningioma, carotid a. aneurysm, or less likely pituitary adenoma. Further eval with MRI brain/pituitary and MRA wwo is recommended. Mild small vessel ischemic changes.
9 CT ANGIO HEAD WWO Redemonstration of soft tissue lesion occupying left sella and perhaps left cavernous sinus. Lesion may contact the left ICA, but is not vascular or aneurysmal in nature. The native pituitary gland is not clearly distinguished, and so the relationship of the lesion to the pituitary gland cannot be determined. The differential diagnosis would include meningioma or primary lesion of pituitary. MRI remains only adequate modality to better assess this lesion.
10 PITUITARY MRI The left half of the pituitary is heterogeneous and enlarged in appearance whereas the right half looks like a partial empty sella. It is conceivable that this may represent a microadenoma in the left half of the pituitary possibly associated with empty sella on the right side. An alternative explanation may be there is a different soft tissue mass in the left half of the sella such as a meningioma or another lesion.
11 BIOCHEMICAL EVALUATION OF PITUITARY AXES Free Testosterone 97 Total Testosterone 271 Ref Range: ng/dl Sex Hormone Binding Globulin 29 Ref Range: nmol/l FSH 5.1 LH 6.4 Prolactin 14.2 Ref range: ng/ml TSH 1.37 Ref range: mcu/ml FT Ref range: ng/dL T3 62 Ref range: ng/dl Insulin-Like Growth Factor 1 Insulin-Like Growth Factor Binding Protein Ref range: ng/ml 6.6 Ref range: Growth Hormone 1.5 Ref range: 0-4.2ng/mL
12 Formal testing with no deficits A1c 5.8 TG 139 Dilated,Non-Ischemic Post-tx BPs < 130/90 NYHA IV
13 ORAL GLUCOSE TOLERANCE TEST WITH GROWTH HORMONE LEVELS Initial Inpatient OGTT 8/28/2013 Time (min) GH Ref range: ng/ml IGF-1 Time (min) Ref range: ng/ml Follow-Up Outpatient OGTT 9/11/2013 GH Ref range: ng/ml Glucose
14 INITIAL MANAGEMENT OF ACROMEGALY Transsphenoidal surgery 1 st line for Intrasellar microadenomas Noninvasive macroadenomas Tumors causing compressive symptoms Surgical removal provides biochemical control with IGF-1 normalization in 75-95% of patients Contraindications to surgery: Patient refusal, severe cardiomyopathy or respiratory disease, or lack of skilled surgeon availability Melmed S, et al. Guidelines for acromegaly management: an update. J Clin Endocrinol Metab. 2009;94(5):
15 OUR PATIENT S HEART SURGICAL CANDIDATE? Cardiology assessment: We discussed the patient at our transplant meeting and agreed that we should proceed with resection. He had his right heart catheterization and biopsy - his hemodynamics are good (just some dehydration). From a cardiac preop point of view, he would not need any other testing done.
16 MANAGEMENT Patient underwent transsphenoidal resection of piutitary microadenoma on 11/4/2013. Given his prolonged history of immunosuppression and prednisone therapy for OHT, it was recommended that he receive stress dose steroids peri-operatively. Post-operatively, he was started on replacement corticosteroids with hydrocortisone 20 mg/10 mg daily.
17 TRANSSPHENOIDAL RESECTION- PATHOLOGY Original H&E No expression of ACTH, TSH, Prolactin, LH, and FSH. Patchy staining for GH Frozen Path 2 soft-tissue adenoma fragments measuring 0.7 and 0.3 cm Fresh multiple fragments from 0.1 to 0.6 cm in size GH Stain Prolactin Stain TSH Stain
18 POST-OPERATIVE EVALUATION 11/5/ :14 (POD #1) 11/6/ :41 (POD #2) TSH /6/2013 Growth Hormone Ref range: (0-4.2 ng/ml) SMC/IGF1 Ref range: ng/ml hour UOP 1785 ml With successful surgery, GH levels typically fall to normal within 1-2 hours (depending on level of elevation before surgery). IGF-1 concentrations fall more slowly, from weeks to months. Feelders RA, et al. Postoperative evaluation of patients with acromegaly: clinical significance and timing of oral glucose tolerance testing and measurement of (free) insulin-like growth factor 1, acid-labile subunit, and growth hormone binding protein levels. J Clin Endocrinol Metab. 2005;90(12):6480.
19 POST-OPERATIVE MANAGEMENT Post-operatively: no visual symptoms, CSF leak, seizures, vomiting. Intermittent nausea. Headaches persist to degree that limiting his activities of daily living. Concern that antirejection drugs may be contributing. Plan for post-operative IGF/GH testing in 3 months. Above will determine need for additional therapy.
20 FOLLOW-UP TESTING SMC/IGF1 Ref range: ng/ml 12/12/ /20/2014 Due to the severity of patient s nausea, he is initially reluctant to undergo repeat OGTT to confirm persistent GH elevation.
21 FOLLOW-UP IMAGING Follow-Up MRA Brain w/o: Broad-based aneurysm arising from the C6 segment of the right internal carotid artery measuring 4 x 4 x 6 mm. Limited examination of the brain.
22 ONGOING MANAGEMENT Glucose Tolerance 2/20/ Growth Hormone Glucose Ref range: (0-4.2 ng/ml) Given the above findings, on 3/13 the patient is started on somatostatin 50 mcg tid with plan to transition to monthly depot somatostatin if tolerates above. Cost and tid injections result in intermittent adherence to therapy. On 8/6, transitioned.
23 BIOCHEMICAL FOLLOW-UP SMC/IGF1 Ref range: ng/ml 12/12/ /20/2014 3/13/2014 4/7/2014 5/22/2014 9/8/
24 ASSESSING FOR CURE Failure to control GH to a normal level is associated with a 3.5 x increased mortality as compared to patients in whom GH is controlled. Mortality in the latter is no different from controls. Giustina A, et al. Criteria for cure of acromegaly: a consensus statement. J Clin Endorinol Metab. 2000;85(2):
25 CONCLUSIONS Elevated serum IGF-1, with a Growth Hormone that fails to suppress after OGTT confirms diagnosis of acromegaly. Surgical resection (transsphenoidal surgery) is first-line treatment for intrasellar microadenomas, noninvasive macroadenomas, and tumors causing compressive symptoms. When surgical control is not achieved, tumor anatomy is unfavorable to surgery, or patient is not a surgical candidate, medical therapies (somatostatin analogues, GHRH antagonists, and dopamine agonists), and radiation therapy can be considered.
26 EXTRA SLIDES
27 DIAGNOSIS OF ACROMEGALY Random GH < 0.4 μg/l and normal IGF-1 excludes acromegaly In a normal patient, serum GH should drop to < 1 ng/ml within two hours after ingestion of a glucose load of 75 g. In an acromegalic patient, post-glucose GH is > 2 ng/ml in > 85% of the time. Jaffe CA, et al. Regulation of GH secretion in acromegaly: reproducibility of daily GH profiles and attenuated negative feedback by IGF-1. J Clin Endocrinol Metab 2001; 86: Giustina A, et al. Criteria for cure of acromegaly: a consensus statement. J Clin Endorinol Metab. 2000;85(2):
28 OPTIONS BEYOND SURGERY
29 CORONAL DYNAMIC (NO POST CONTRAST CORONAL DONE)
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