Blackwell's underground clinical vignettes. Biochemistry [3rd ed] 0632045450, 9780632045457

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BLACKWELL'S UNDERGROUND CLINICAL VIGNETTES

BIOCHEMISTRY, 3E VIKAS BHUSHAN, MD University of California, San Francisco, Class of 1991 Series Editor, Diagnostic Radiologist

V1SHAL PALL, MBBS Government Medical College, Chandigarh, India, Class of 1996 Series Editor, U. of Texas, Galveston, Resident in Internal Medicine & Preventive Medicine

TAO LE, MD University of California, San Francisco, Class of 1996

JOSE M. FIERRO, MD La Salle University, Mexico City

HOANG NGUYEN, MD, MBA Northwestern University, Class of 2001

b

Blackwell Science

CONTRIBUTORS Tisha Wang University of Texas Medical Branch, Class of 2002 Fadi Abu Shahin, MD University of Damascus, Syria, Class of 1999 Vipal Soni, MD UCLA School of Medicine, Class of 1999

© 2002 by Blackwell Science, Inc.

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2001004933

Notice The authors of this volume have taken care that the information contained herein is accurate and compatible with the standards generally accepted at the time of publication. Nevertheless, it is difficult to ensure that all the information given is entirely accurate for all circumstances. The publisher and authors do not guarantee the contents of this book and disclaim any liability, loss, or damage incurred as a consequence, direct h or indirectly, of the use and application of any of the contents of this volume.

CONTENTS Acknowledgments Preface to the 3rd Edition How to Use This Book Abbreviations

x xiii xvi xvii

Endocrinology

17-Alpha-Hydroxylase Deficiency 5-Alpha-Reductase Deficiency Acromegaly Addison's Disease Bartter's Syndrome Congenital Adrenal Hyperplasia Diabetes Insipidus Diabetic Ketoacidosis Glucagonoma Hirsutism—Idiopathic Hyperaldosteronism—Primary Hypercalcemia Hyperparathyroidism—Primary Hyperthyroidism (Graves' Disease) Hypocalcemia from Pancreatitis Hypokalemia Hypomagnesemia Hyponatremia Insulinoma Kallmann's Syndrome Kwashiorkor Lactic Acidosis Metabolic Alkalosis Nonketotic Hyperosmolar Coma Osteomalacia Pheochromocytoma Precocious Puberty Pseudohypoparathyroidism Rickets SIADH Thyroid Storm Vitamin A Deficiency Vitamin B, Deficiency (Beriberi) Vitamin B3 Deficiency (Pellagra) Vitamin C Deficiency (Scurvy) Vitamin K Deficiency Carcinoid Syndrome Crigler-Najjar Syndrome

Gastroenterology

B3

m m

m

Genetics

Hematology/Oncology

Dubin-Johnson Syndrome Gilbert's Disease Wilson's Disease Acute Intermittent Porphyria Albinism Alkaptonuria Cystic Fibrosis Cystinuria Ehlers-Danlos Syndrome Fabry's Disease Familial Hypercholesterolemia Familial Hypertriglyceridemia Fanconi's Anemia Fragile X Syndrome Galactosemia Gaucher^ Disease Hereditary Fructose Intolerance Homocystinuria Hunter's Disease Hurler's Disease Kartageners Syndrome Klinefelter's Syndrome Krabbe's Disease Lesch-Nyhan Syndrome Maple Syrup Urine Disease Metachromatic Leukodystrophy Niemann-Pick Disease Orotic Aciduria Phenylketonuria (PKU) Phosphoenolpyruvate Carboxykinase Deficiency Pompe's Disease Porphyria Cutanea Tarda Pyruvate Kinase Deficiency Tay-Sachs Disease von Gierke's Disease Xeroderma Pigmentosum Anemia—Folate Deficiency Anemia—Iron Deficiency Anemia—Vitamin B12 Deficiency Glucose-6-Phosphate Dehydrogeri ase Deficiency Hemophilia, Type A Hereditary Spherocytosis

m m

Eil

Etil

m IUI

m BEI 133

m m m m EH m m m m m m m üi

m m

EE1

Neph rology/Urology Neurology Gynecology

Orthopedics Psychopharmacology Pulmonary

Rheumatology

Methemoglobinemia Paroxysmal Nocturnal Hemoglob inuria Renal Tubular Acidosis Rhabdomyolysis Duchenne's Muscular Dystrophy Wernicke-Korsakoff Syndrome Primary Amenonhea—Testiculai Feminization Secondary Amenorrhea Osteogenesis Imperfecta Antabuse Effect Hyaline Membrane Disease Alpha-1-Antitrypsin Deficiency Hyperventilation Carbon Monoxide Poisoning Gout

m EH

m m

E3

m B3

133

m

EQ

ES ES EH EH

ACKNOWLEDGMENTS T h r o u g h o u t the p r o d u c t i o n of Ulis book, we have had the snj> port of many friends a n d colleagues. Special thanks to out support team including A n n Gupta, .Andrea Fellows, Anastasia Anderson, Srishti Gupta, Mona Pall, J o n a t h a n Kirsch a n d Chirag Amin. For prior contributions we t h a n k Gianni Le Nguyen, Tarun Mathur, Alex G r i m m , Sonia Santos a n d Elizabeth Sanders. We have enjoyed working with a world-class international p u b lishing g r o u p at Blackwell Science, including Laura DeYoung, Ann Nuttbrock, Lisa Flanagan, Shawn Girsberger, L o r n a H i n d a n d G o r d o n TibbitLs. For help with securing images for the entire series we also t h a n k Lee Martín, Kristopher J o n e s , Tina Panizzi and Peter A n d e r s o n at the University of Alabama, the A r m e d Forces Institute of Pathology, a n d many of o u r fellow Blackwell Science a u t h o r s . For submitting c o m m e n t s , corrections, editing, proofreading, a n d assistance across all of the vignette titles in all editions, we collectively lliank: Tara Adamovich, Carolyn Alexander, Kris Alden, H e n r y E. Aryan, Lynman Bacolor, Natalie Barteneva, Dean Bartholomew, Debashish Behera, Sumit Bhatia, Sanjay Bindra, Dave Brinton, J u l i a n n e Brown, Alexander Brownie, Tamara Callahan, David Canes, Biyan Casey, Aaron Caughey, Hebert Chen, J o n a t h a n Cheng, Arnold C h e u n g, Arnold Chin, Simion Chiosea, Yoon Cho, Samuel C h u n g , G l e i c h e n C o n a n t , Vladimir Coric, C h r i s t o p h e r Gosgrove, Ronald Cowan, Karekin R. C u n n i n g h a m , A. Sean Dalley, Rama D a n d a m u d i , Sunit Das, Ryan A r m a n d o Dave, J o h n David, E m m a n u e l tie la Cruz, Robert DeMello, Navneet Dhillon, Sharmila Dissanaike, David Donson, Adolf Etchegaray, Alea Ensebio, Priscilla A. Frase, David F r e n / , Kristin Gaumer, Yohannes Gebreegziabher, Anil Gehi, Tony George . I..M. ( lumntti, Parul Goyal, Alex G r i m m , Rajeev Gupta, A h m a d Halim, Sue Hall, David Hasselbacher, Tamra H e i m e r t , Michelle Higley, Dan Hoit, Eric Jackson, Tim Jackson, S u n d a r j a y a r a m a n , P e i - N i j o n e , Aarchan Joshi, Rajni K. Julia, Faiyaz Kapadi, Seth Karp, Aaron S. Kesselheim, Sana Khan, Andrew Pin-wei Ko, Francis Kong, Paul Konitzky. Warren S. Krackov, Benjamin H.S. Lau, Ann LaCasce, C o n n i e Lee, Scott Lee, Guillermo L e h m a n n , Kevin L e u n g . Paul Levetl, Warren Levinson, Eric Ley, Ken Lin,

Pavel Lobanov. J. Mark Maddox , Aram Mardian, Samir Mehta, Gil Melmed. J o e Messina, Robert Mosca, Michael Murphy, Vivek Nandkarni, Siva Naraynan, Gai"vell Nguyen, Linh Nguyen, D e a n n a Nobleza, Craig Nodurft, Ge o rg e N o u m i , Darin T O k u d a , Adam L. Palance, Paul P a m p h r u s , J i n h a Park, Sonny Patel, Ricardo Pietrobon, Riva L. Rahl, Aashita Randeria, Rachan Reddy, Bcatriu Rcig, Marilou Reyes. J e r e m y R i c h m o n , Tai Roe, Rick Roller, Rajiv Roy, Diego Ruiz, A n t h o n y Russell, Sanjay Sahgal, U m i i m a l a Sarkar, J o h n Schilling, Isabell Schmitt, Daren Schuhmacher, Sonal Shah, Fadi Abu Shahin, Mae SheikhAli, Edie Shen. Justin S m i t h , J o h n Stulak, Lillian Su, Julie S u n d a r a m , Rita Suri, Seth Sweetser, A n t o n i o Talayero, Merita Tan, Mark Tanaka, Eric Taylor, Jess T h o m p s o n , Indi T r e h a n , Raymond Turner, Okafo L c h e n n a , Eric L y g u a n c o , Richa Varma, J o h n Wages, Alan Wang, Eunice Wang, Andy Weiss, Amy Williams, Brian Yang, H a i n Zaky, Aslu ;tf Zaman a n d David Zipf. For generously c o n i r i b u i i n g images to the entire Underground Clinical Vignette Step 1 series, we collectively t h a n k the staff at Blackwell Science in Oxford, Boston, a n d Berlin as well as: • Axford, J. Medicine. Osney Mead: Blackwell Science Ltd, 1996. l i g u r e s 2.1 I, 2.15, 2.16, 2.27, 2.28, 2.31, 2.35, 2.36, 2.38, 2.43, 2.65a, 2.65b, 2.65c, 2.103b, 2.105b, 3.20b, 3.21, 8.27, 8.27b, 8.77fe, 8.77c, 10.81b. 10.96a, 12.28a, 14.6, 14.16, 14.50. •

Bannister B, Begg N, Gillespie S. infectious Disease, 2'"' Edition. Osney Mead: Blackwell Science Ltd, 2000. Figures 2.8, 3.4, 5.28, 18.10, W5.32.W5.6.

•

Berg D. Advanced Clinical Skills and Physical Diagnosis. Blackwell Science Ltd., 1999. Figures 7.10, 7.12, 7.13, 7.2, 7.3, 7.7, 7.8. 7.9. 8.1, 8.2, 8.4, 8.5, 9 . 2 , 1 0 . 2 , 1 1 . 3 , 11.5, 12.6.

•

Cuschieri A, Hennessy TPJ, G r e e n h a l g h RM, Rowley DA, Grace PA. Clinical Surgery. Osney Mead: Blackwell Science Ltd, 1996. Figures 13.19, 18.22, 18.33.

•

Gillespie SH, Bamford K. Medien/ Micml/iology and Infection at 2) has over 125 color plates, including patient images, dermatology, a n d fundtiscopy.

Each adas image is descriptively c a p t i o n ed a n d linked to its corr e s p o n d i n g Step 1 case, Step 2 case, a n d / o r Step 2 MiniCase.

How Atlas Links Work: Step 1 Book Codes are: A - Anatomy Step 2 Book Codes are: ER - Emergen:y Medicine IM1 = Internal Medicine. Vol. 1 BS = Behavioral Science IM2 = Internal Medicine. Vol. II BC = Biochemistry NEU = Neurology Ml = Microbiology, Vol. I OB = OB/GYN M2 = Microbiology, Vol. 11 PED = Pediatrics PI = Pathophysiology, Vol. I SUR = Surgery P2 = Pathophysiology, Vol. II PSY=Psyrhhiny P3 = Pathophysiology, Vol. Ill MC B MiniCasê PH = Pharmacology Case Number

M-P3-032A

I "I I I I ER-035A, ER-035B

Indicates Type of Image: 11 = 1 tematology M - Microbiology PG = Gross Pathology PM = Microscopic Pathology

Indicates UCV1 or UCV2 Series

If ihe Case n u m b e r (032, 035, etc.) is n o t followed by a letter, then t h e r e is only o n e image. Otherwise A, B, C, D indicate u p to 4 images. Bold Faced Links: In o r d e r to give you access to the largest n u m b e r of images possible, we have chosen to cross link the Slep 1 a n d 2 series. If the link is bold-faced this indicates that the link is direct (i.e.. Step 1 Case with the Basic Science Step 1 Adas link). [f t h e link is not bold-faced diis indicates that the link is indirect (Step 1 case with Clinical Science Slep 2 Atlas link o r vice versa). We have also i m p l e m e n t e d a few structural c h a n g es u p o n your request: Each c u r r e n t a n d future edition of o u r p o p u l a r First Aid for the USMLEStep 1 (Appleton & Lange/McGraw-Hill) a n d Eirsl Aid jorthe USMLEStep 2 (Appleton & Lange/McGraw-Hill) book will be linked to di e c o r r e s p o n d i n g UCV case. We eliminated UCV —* First Aid links as they frequendy b e c o m e out of date, as the First Aid books are revised yearly.

•

T h e Color Adas is also specially designed for quizzing— captions are descriptive a n d d o not give away the case n a m e

directly, We h o p e die u p d a t e d UCV series will remain a u n i q u e a n d wellintegrated study tool that provides c o m p a c t clinical correlations to basic science information. They are designed to be easy a n d fun (comparatively) to read, a n d helpful for b o t h licensing exams a n d the wards. We invite your corrections a n d suggestions for the fourth edition of these books. For the first submission of each factual correction or new vignette that is selected for inclusion in the fourth edition, you will receive a personal acknowledgment in the revised book. If you submit over 20 high-quality corrections, additions or new vignettes we will also consider inviting you to b e c o m e a " C o n t r i b u t o r " o n the b o o k of your choice. If you are interested in b e c o m i n g a potential "Contributor" or "Author" o n a future UCV book, o r working with o u r team in developing additional books, please also e-mail us your C V / r e s u m e . We prefer that you submit corrections o r suggestions via electronic mail to UCVteam(ö)yahoo.coni. Please include " U n d e r g r o u n d Vignettes" as the subject of your message. If you d o not have access to e-mail, use d i e following mailing address: Blackwell Publishing, Attn: UCV Editors, 350 Main Street, Maiden, MA 02148, USA. Vikas Bhushan Visitai Pall Lao Le O c t o b e r 2001

HOW TO USE THIS BOOK This series was originally developed to address the increasing number of clinical \ignette questions on medical examinations, including the USMLE Step 1 and Step 2. It is also designed to supplement and complement the popular First Aid for the USMIJi Step I (Appleton & Lange/McGraw Hill) and First Aid for the USMlJiStep 2 (Appleton & Lange/McGraw Hill). Each UCV 1 book uses a series of approximately 100 "supraprototypical" cases as a way to condense testable facts and associations. The clinical vignettes in this series are designed to incorporate as many testable facts as possible into a cohesive and memorable clinical picture. The vignettes represent composites drawn from general and specialty textbooks, reference books, thousands of LISMLE style questions and the personal experience of* die authors and reviewers. Although each case tends to present all the signs, symptoms, and diagnostic findings for a particular illness, patients generally will not present with such a "complete" picture either clinically or on a medical examination. Cases are not meant to simulate a potential real patient or an exam vignette. All the boldfaced "buzzwords" are for learning purposes and are not necessarily expected to be found in any one patient with the disease. Definitions of selected important terms are placed within the vignettes in (s.MAiX CAPS) in parentheses. Odier parenthetical remarks often refer to the pathophysiology or mechanism of disease. The format should also help students learn to present cases succincdy during oral "bullet" presentations on clinical rotations. The cases are meant to serve as a condensed review, not as a primary reference. The information provided in this book has been prepared with a great deal of thought and careful research. This book should not, however, be considered as your sole source of information. Corrections, suggestions and submissions of new cases are encouraged and will be acknowledged and incorporated when appropriate in future editions.

ABBREVIATIONS 5-ASA ABGs ABVD ACE ACTH ADH All' AI AIDS Al 1 ALT AMI. ANA ARDS ASD ASO AST AV BE BP BUN CAD GALLA CBC CHF CK CLL CML ( i.VIV CNS COPD CPK CSF CT (\\ CXR DIC DIP DKA DM DTRs DVT

5-aminosalicylic acid arterial blood gases adriamycin/bleomycin/vincristine/dacarbazine angiotensin-converting enzyme adrenocorticotropic h o r m o n e antidiuretic h o r m o n e alpha fetal protein aortic insufficiency acquired immunodeficiency sy n d r o me acute lymphocytic leukemia alanine transaminase acute myelogenous leukemia antinuclea r antibody adult respiratory distress s y n d r o m e atrial septal defect anti-streptolysin O aspartate transaminase arteriovenous barium e n e m a blood pressure blood u r e a n o t r o g e n coronary artery disease c o m m o n acute lymphoblastic leukemia antigen c o m p l e t e blood c o u n t congestive h e a r t failure creatine kinase c h r o n ic lymphocytic leukemia chronic myelogenous leukemia cytomegalovirus central nervous system c h r o n i c obstructive p u l m o n a r y disease creatine Phosphoki na se cerebrospinal fluid c o m p u t e d t o m o g r a p hy cerebrovascular accident chest x-ray disseminated intravascular coagulation distal interphalangeal diabetic ketoacidosis diabetes mellitus d e e p t e n d o n reflexes d e e p venous thrombosis

EBV ECG Echo EF EGD EMG ERCP ESR FEV FNA FTA-ABS I'A( : GFR GH GI GM-CSF

Epstein—Barr virus electrocardiography e c h o c a r d i o g r a p hy ejection fraction esophagogastroduodenoscopy electromyography endoscopi c r e U o g r a d e c h o l a n g i o p a n c r e a t o g r a p h y erythrocyte sedimentation rate forced expiratory volume fine n e e d l e aspiration fluorescent t r e p o n e m a l antibody absorption forced vital capacity g lo m eru la r filtration rate growth h o r m o n e gastrointestinal granulocyte m a c r o p h a g e colony stimulating

factor GU HAV hcG HEENT HIV HLA HPI HR HRIG HS ID/CC IDDM Ig IGF IM JVP KU B LDH LES LFTs LP LV LVH Lytes MCHC M( Y MEN

genitourinary hepatitis A virus h u m a n chorionic g o n a d o t r o p h i n head, eyes, ears, nose, a n d throa t h u m a n immunodeficiency virus h u m a n leukocyte antigen histoiy of p r e s e n t illness heart rate h u m a n rabies i m m u n e globulin hereditary spherocytosis identification a n d chief complain t insulin-dependen t diabetes mellitus immunoglobulin insulin-like grovrth factor intramuscular j u g u l a r venous pressure kidneys/ureter/bladder lactate d e h y d r o g e n a se lower esophageal sphincter liver function tests lumbar puncture left ventricular left ventricular hypertroph y electrolytes m e a n corpuscular h e m o g l o b i n c o n c e n t r a t i o n m e a n corpuscular volume multiple e n d o c r i n e neoplasia

MGLTS Ml l( MI MOPP MR NHL NIDDM NPO XSAID PA PIP PBS PE PFTs I'M I PMN FT PTCA Pill PTT PUD RBC RPR RR RS RV RV11 SBFT S IAD H SLE STD TFTs tPA TSH TIBC TIPS TPO TSH TTP UA UGI US

m o n o c l o n a l g a m m o p a t h y of u n d e t e r m i n e d significance major histocompatibiliry comple x myocardial infarction n i e c h l o r e t h a m i n e / v i n c i i s t i ne ( O n c o v o r i n ) / procarbazine/prednisone magnetic r e s o n a n ce (imaging) non-Hodgkin' s l y m p h o m a n o n - i n su l i n - d e p e n d e nt diabetes mellitus nil p e r os ( n o t h i n g by m o u t h ) nonsteroidal anti-inflammatory d r u g posteroanterio r proximal interphalangcal peripheral blood smear physical exam p u l m o n a r y function tests point of maximal intensity p o l y m o r p h o n u c l e a r leukocyte p r o t h r o m b i n lime p e r c u t a n e o u s transluminal angioplasty parathyroid h o r m o n e partial thromboplastin lime peptic ulcer disease red blood cell rapid plasma reagin respiratory rate R c e d - S t e r n b e r g (cell) right ventricular right ventricular hypertrophy small bowel follow-through syndrom e of i n a p p r o p r i a t e secretion of ADH systemic lupus erythematosus sexually transmitted disease thyroid function tests tissue plasminogen activator thyroid-stimulating h o r m o n e total iron-binding capacity iransjugular intrahepatic portosystemic s h u n t thyroid peroxidase thyroid-stimulating h o r m o n e thromboti c thrombocytopenic p u r p u r a urinalysis u p p e r GI ulirasound

VDRL VS VT WBC WPW XR

Venereal Disease Research Laboratory vital signs ventricular tachycardia white blood cell Wolff-Parkinson-White (syndrome) x-ray

ID/CC

A 16-year-old girl is referred to an endocrinologist owing to lack of menses (PRIMARY AMENORRHEA) and absence of pubic hair, axillary hair, and breast development (LACK OF SECtj »NDARV SEXUAL CHARACTERISTICS).

H PI

She also complains of frequent headaches and ringing in her ears (due to hypertension). o

PE

Labs

VS: hypertension (BP 160/105). PE: funduscopic exam normal; no lymphadenopathy; no hepatosplenomegaly; absence of breast tissue; no abdominal or pelvic masses palpable; no axillary or pubic hair; vulvar labia normal. Lvtes: hypokalemia; hypernatremia. ABGs: metabolic alkalosis (due to mineralocorticoid action of 11-deoxycorticosterone and cortilrosterone). Suppressed renin; increase in urinary gonadotropins (due to attempt to compensate for lack of sex hormones); diminished 17-ketosteroids (product of sex hormones); increased progesterone, pregnenolone. 11-deoxycorticosterone, and corticosterone.

Treatment

Glucocorticoids. Sex hormones.

Discussion

A decrease in 17-a-hydroxylase produces an increase in 11deoxycorticosterone and corticosterone (due to shifting metabolism of sex hormones to aldosterone pathway); renin is suppressed (due to aldosterone negative feedback). Females fail to develop secondary sexual characteristics; males develop ambiguous external genitalia (MALE PSEUDOHERMAPHRODITISM).

17-ALPHA-HYDROXYLASE DEFICIENCY

o Cl

II

ID/CC

A neonatal boy is brought to the pediatrician by his father, who recendy discovered that his son does not urinate through his penis.

HPI

The patient's father also reports that he cannot find his son's testes (due to cryptorchidism).

PE

Penis small for age (MlCROPHMTJA); testes located in inguinal canal bilaterally (CRYPTORCHIDISM); urinary meatus lies in perineum (HYPOSPADIAS); scrotal sac bifid.

Labs

Imaging

Markedly reduced dihydrotestosterone with normal testosterone level. Decreased 5-a-reductase activity. Pelvic US: confirms cryptorchidism and absent uterus.

Treatment

Psychosocial support. Gender assignment. Consider appropriate hormonal replacement therapy.

Discussion

An autosomal-recessive disorder of virilization affecting genetic males. 5-a-reductase converts testosterone to dihydrotestosterone. Lack of type 2 isozyme of 5-alpha-reductase produces a decrease in dihydrotestosterone, which is responsible for virilization of the external genitalia.

5-ALPHA-REDUCTASE DEFICIENCY

ID/CC

A 43-year-old white male comes to die e m e r g e n c y r o o m complaining of severe retro-orbital headache ( b e h i n d his eyes) along with blurred vision.

H PI

H e also complains of weakness over the past few m o n t h s and an increase in hat size as well as an inability to wear his wedding ring (due to growth in finger width). His family also notes a coarsening of his facial feat tires and deepening of his voice.

PE

VS: hypertension (HP 150/100). PE: skin thick a n d oily; prominent forehead and jaw; e n l a r g e d t o n g u e a n d widening gaps between teedi: large hands and feet; bitemporal hemianopsia; cardiomegaly; hepatosplenomegaly.

Labs

Hyperglycemia; h y p e r p h o s p h a t e m i a; increased IGF-1; increased levels of GH that fail to suppress after oral glucose load. L'A: increased urinary calcium.

Imaging

XR: thickening of skull; erosion and enlargement of sella turcica: widening distal phalanges in h a n d s a n d feet. MR, h e a d : enlarged pituitary gland c o n t a i n i n g a 2 cm mass.

Gross Pathology

Acidophilic a d e n o m a of pituitary gland with ill-defined capsule exerts mass effects o n pituitary a n d nearby optic chiasm; t u m o r rarely malignant.

Micro Pathology

Densely packed, m a t u r e cells that arc highly granulocytic a n d eosinophilic; stains highly for G H .

Treatment

Transsphenoidal microsurgical a d e n o m e c t o m y is the t r e a t m e n t of choice; radiotherapy to r e d u c e further growth of tumor. Medical therapy with octreotide a n d / o r b r o m o c r i p t i n e if surgery fails or is contraindicated .

Discussion

T h e most c o m m o n cause of acromegaly is pituitary adenoma. If excess GH secretion is present in childhood, gigantism appears; in adults, acromegaly appears. H e a d a c h e a n d j o i n t pain are early complaints; b l u r r ed vision and visual-field change s occur later. Almost every organ in the body increases in size; 2 5 % of patients exhibit glucose intolerance. Visual field changes (e.g., bitemporal hemianopsia) may occur secondary to compression of the nerves of the optic chiasm by die tumor.

Atlas Links

U

ACROMEGALY

_J

PM-BC-003

MC-084

ID/CC

A 37-year-old female is admitted to the internal medicine ward for evaluation of increasing weakness and intermittent episodes of dizziness, nausea, and vomiting related to stress and exercise.

HPI

She is a vegetarian, takes no drugs or medications, and does not drink alcohol or smoke cigarettes. She reports an excessive craving for salty foods such as chips and salted peanuts.

PE

VS: tachycardia (HR 110); hypotension (BP 90/65). PE: thin with dry mucous membranes; pigmentation of buccal mucosa and palms of hands; no neck masses; chest auscultation normal; no abdominal masses; no hepatosplenomegaly; no lymphadenopathy.

Labs

CBC: normal. Lvtes: hyponatremia; hyperkalemia. Glucose low; increased BUN with normal creatinine; amylase and LFTs normal; high ACTH; low Cortisol.

Treatment

Glucocorticoid and mineralocorticoid hormones. Hydrocortisone on an emergent basis.

Discussion

Primary hypoadrenalism (ADDISON'S DISEASE) may be caused by autoimmune mechanisms, tuberculous infection, or sudden discontinuation of chronic steroid adminisUation. Secondary hypOadrenalism is due to abnormalities of hypothalarnic-pituitary function.

ADDISON'S DISEASE

1

ID/CC

A 15-year-old female is admitted to the hospital for evaluation of persistent weakness for the last 6 months dial has been unresponsive to multivitamin treatment.

H PI

She denies allergies, surgeries, psychological problems, transfusions, drug use, or any relevant past medical history. i^B

PE

Labs

Micro Pathology

VS: heart rate normal; no fever; normal BP (excludes primary hyperaldosteronism). PE: well hydrated; pupils equal and reactive to light and accommodation; no neck masses; no lymphadenopathy; chest normal; abdomen soft and nontender; no masses; neurologic exam normal; no peripheral edema; sexual development appropriate for age. CBC: normal. Lytes: hyponatremia; hypokalemia. ABGs: metabolic alkalosis. Increased plasma renin (excludes primary hyperaldosteronism); increased urinary excretion of prostaglandins. Juxtaglomerular cell hyperplasia on renal biopsy.

Treatment

Indomethacin to decrease prostaglandin synthesis. Potassium chloride supplements and potassium-sparing diuretics.

Discussion

liartter's syndrome is a hereditary disorder characterized by a defective Na'-K + -2Cr cotransporter in the thick ascending loop of Henle. This results in an impaired reabsorptive conservation mechanism of sodium (due to end-organ resistance to angiotensin), with urinary sodium wasting and a consequent increase in renin production (through increased renal prostaglandins). Therefore, there is an increase in aldosterone activity with hypokalemic alkalosis. Hypokalemia perpetuates the cycle by stimulating renin activity.

BARTTER'S SYNDROME

o

O CD

ID/CC

A n e w b o rn is evaluated by a n e o n a t o l o g y because die inter n who p e r f o r m e d t he delivery cannot tell whether the child is male o r female (AMBIGUOUS GENITALIA).

HPI

PE

T h e child is also lethargic a n d lacks sufficient strength to suck o n m o t h e r ' s milk adequately ( d u e to salt wasting). A m b i g u o us external genitalia; increase in size of clitoris; fusion of labia to th e poin t of resembling scrotal sac.

Labs

Lvtes: hyponatremia; hyperkalemia. Increase in 17-a-OH progest e r o n e a n d its metabolite, pregnanetriol; increase in urinary 17-ketosteroids (defect is distal to 17, 20-desmolase); elevated s c r u m A C T H . Prenatal diagnosis is possible at 14 to 16 weeks (due to increase in 17-a-OH p r o g e s t e r o n e ) . Karyotype: 46,XX female.

Treatment

Cortisol, d e h y d r o c o r t í c o s t e r o n e acetate if salt wasting is present.

Discussion

Lack of 2l-hydroxyla.se causes a decrease in Cortisol with a cons e q u e n t increase in A C T H , which in turn p r o d u c e s hyperplasia of the adrenals—resulting in an increase in a n d r o g e n p r o d u c tion that gives rise to signs of female p s e u d o h e r m a p h r o d i t i s m (as in this case) o r enlarged genitalia in t h e male. May occur with or without salt wasting.

CONGENITAL ADRENAL HYPERPLASIA

ID/CC

A 2/-year-old white male complains of excessive thirst (POLYDIPSIA) and increased urination (POLYURIA) with very diluted urine.

HPI

The patient drinks several liters of water every day. He was well until this time. The patient also admits to frequent urination (including nocturia) of large volumes that are clear and watery.

PE

VS: slight tachycardia. PE: mild dryness of mucous membranes; visual field testing normal; no papilledema; pupils equal and reactive.

Labs

Low urine specific gravity (< 1.006); low urine osmolarity (< 200 mOsm/L); elevated serum osmolality (> 290 mOsm/L); hypernatremia; water deprivation test demonstrates inability to concentrate urine widi fluid restriction (urinary osmolality continues to be low).

Imaging

CT: may show masses or lesions in hypothalamus.

Treatment

Central (primary) diabetes insipidus: intranasal desmopressin, diuretics and ADH-releasing dings such as chlorpropamide. carbama/.epine and Clofibrate. Nephrogenic (secondary) diabetes insipidus: add indomethacin, amiloride, a nd/ or hydrochlorothiazide.

Discussion

Diabetes insipidus is caused by an ADH deficiency (PRIMARY) or by renal unresponsiveness to ADH (NEPHROGENIC OR SECONDARY). Primary diabetes insipidus can be caused by surgical, traumatic, or anoxic damage to the hypothalamus or pituitary stalk during pregnancy (SHEEHAN'S SYNDROME). Deficiency of ADH results in renal loss of free water and hypernatremia.

DIABETES INSIPIDUS

ID/CC

A 28-year-old seamstress is a d m i t t ed to the interna l medicine ward because of malaise, confusion, abdominal pain, vomiting, a n d diarrhea.

HPI

She is a known insulin-dependent diabetic (IDDM type I, juvenile o n s e t ). O n e day before h e r admission, she went o u t to celebrate her birthday a n d drank alcohol until she became intoxicated (she also forgot to administer insulin).

PE

VS: tachycardia (HR 92); hypotension (BP 9 0 / 5 0 ) ( d u e to hypovolemia): rapid, d e e p breathing (KUSSMAUL RESPIRATION). PE: dehydration; pe ri phe ral cyanosis; cold, dry skin; peculiar fruity breath smell (due to k e t o n e bodies, acetoacetate, a n d ß-OHbutvrate).

Labs

CBC: leukocytosis (14,000) (without infection). Lytes: hyponatremia (130 m E q / L ) . ABGs: markedly r e d u c e d bicarbonate (10 m E q / L ) ; acidosis ( p H = 7.1). Increased ketones in blood; increased creatinine; hyperglycemia; increased anion gap (between 10 a n d 18) (anion g a p is calculated as follows: [Na + K]-[C1 + HCO3]); increased amylase (without pancreatitis). UA: glycosuria; ketonui ia.

Treatment

Nasogasuic tube, correction of fluid deficit (caution owing to risk of p r o d u c i n g cerebral e d e m a ) . Potassium. Gradual lowering of glucose with insulin.

Discussion

Keioacidosis might b e the first manifestation of diabetes. It is m o r e c o m m o n in i n s u l i n - d e p e n d e nt diabetics than hyperosmolar coma. It usually follows a period of physical or menta l stress (e.g., MI, acute grief) or infection.

DIABETIC KETOACIDOSIS

ID/CC

A 58-year-old white female comes to see h e r internist because of the development of polyuria, polydipsia (due to hyperglycemia), a n d a skin e r u p t i o n that conies a n d goes in different parts of h e r bodv ( M I Koi.vnc MIGRATOÂYRASH).

HPI

She also complains of increasing i n t e r m i t t e nt diarrhea, nausea, vomiting, weight loss, and occasional weakness a n d dizziness.

PE

VS: n o r m a l . PK: patient well hydrated; marked pallor; erythematous rash o n anterior chest, legs, and arms ; n o neck masses; lungs clear to auscultation; h e a rt s o u n d s rhythmic; a b d o m e n soft; n o masses; n o peritoneal signs; n o lymphadenopathy.

Labs

Imaging

CBC: a n e m i a ( H b 7.4 m g / d L ) . Markedly increased s e r u m glucagon levels; hyperglycemia. M R / C T : 2.5-cm e n h a n c i n g mass in body a n d tail of pancreas; several liver metastases.

Treatment

Surgical removal. Streplozocin if metastatic; insulin; prophylactic heparin a n d zinc (for skin rash); octreotide.

Discussion

G l u c a g o n o m a i s a pancreatic islet cell neoplasm (of a cells) that secretes abnormally high a m o u n t s of glucagon with resulting symptomatic hyperglycemia; it may also secrete gastrin, A C T H , a n d serotonin. Glucagonomas arise from a 2 islet cells in die pancréas, a n d the majority ( > 70%) are malignant. G l u c a g o n o m as may also be associated with multiple e n d o c r i n e neoplasia (MEN) type I.

Atlas Links

J

GLUCAGONOMA

U

PM-BC-009A, PM-BC-009B

ID/CC

HPI

A 24-year-old woman is referred to the endocrinologist because of concern over excessive facial hair along with hair on her central chest and thighs. The patient's menses are regular, with an average flow lasting 3 to 4 days. She is not taking any drugs.

PE

Hirsutism noted; no clitoromegaly present (no evidence of virilization); no abdominal or pelvic mass palpable per abdomen or per vagina.

Labs

Normal total testosterone levels; normal DHEAS; normal urine for 17-ketosteroids.

Imaging

US, abdomen and pelvis: both adrenals and ovaries normal.

Treatment

No therapy required.

Discussion

Hirsutism that is disproportionate to the patient's ethnic background and is accompanied by normal periods is termed idiopathic. If testosterone and DHEAS levels are normal, the patient can be reassured that the condition is benign. If the onset of hirsutism is pubertal with irregular periods, the possibility of polycystic ovarian syndrome exists. Recent-onset hirsutism in an adult female, especially when associated with amenorrhea, requires complete investigation to exclude an adrenal or ovarian tumor.

HIRSUTISM—IDIOPATHIC

ID/CC

HPI PE

A 39-year-old woman is referred to an internist by h e r family practitioner because of persistent hypertension that has b e e n unresponsive to conventional treatment: she also complains of profound muscle weakness ( d u e to hypokalemia) . She i*- a two-pat k-a-day smoker who drinks occasionally. VS: n o r m a l heart rate; hypertension (BP 2 0 0 / 1 0 0 ) . PE: n o pallor; retinal h e m o r r h a g e s , e x u d a t e s, a n d AV nicking: lungs clear; n o hear t m u r m u r s ; a b d o m e n soft; n o palpable masses; n o lymph-

adenopathy. Labs

Imaging

Micro Pathology

CBC: increased hematocrit. Lytes: hypokalemia; h y p e r n a t r e m i a (secondary to hyperaldosteronism) . ABGs: high s e r u m bicarbonate. Glucose n o r m a l (vs. ectopic A C T H p r o d u c t i o n ) . ECG: left ventricular hypertrophy a n d strain. UA: n o proteinuria. Aldosterone leveLs high; renin levels low (primary hyperaldosteronism). C T / M R : 1.7-cm e n h a n c i n g left adrenal mass. NP-59 iodocholesterol scintigraphy positive. Adrenal venous sampling shows > 1 0 : 1 ratio of aldosterone o n the left versus right. Glomerulosa-cell benign adrenal a d e n o m a .

Treatment

Left adrenalectomy.

Discussion

Primary hyperaldosteronism typically presents with hypertension, hypokalemia, h y p e r n a t r e m i a, a n d increased bicarbonate d u e to increased secretion of aldosterone by an adrenal aden o m a ( C O N N ' S SYNDROME) o r hyperplasia. Hypertension is characteristically unresponsive to ACE inhibitors. Surgically correctable causes of hypertension include C o n n ' s syndrome , p h c o c h r o m o c y t o m a , renal artery stenosis, a n d coarctation of the aorta.

HYPERALDOSTERONISM —PRIMARY

ID/CC

H PI

PE

A 55-year-old m e n o p a u s al female comes to see heil internist because of progressive constipation a n d excessive urination over the past 2 m o n t h s ; she also complains of palpitations both at rest a n d d u r i n g exercise. She has read "all a bout" osteoporosis d u r i n g m e n o p a u s e a n d is afraid of developing it, so she has b e e n taking a b u n d a n t calcium s u p p l e m e n t s a n d vitamin D injections. VS: heart rate 80 with skipped beats h e a r d (VENTRICULAR EXTRASYS TOLES) . PE: lungs clear; n o neck masses; thyroid n o t palpable; n o lymphadenopathy ; muscle weakness with hyporeflexia; a b d o m e n soft with decreased bowel sounds; n o masses; n o a b n o r m a l pigmentation; soft tissue calcification in skin of arms a n d legs.

Labs

Markedly increased s e r u m calcium (12 m g / d L ) (always correct calcium level for s e r u m a l b u m i n ) . P h o s p h o r u s n o r m a l (makes primary hyperparathyroidism less likely). ABGs: metabolic alkalosis. Increased BUN. ECG: shor t Q-T. No PTH-related protein d e t e c t e d.

Treatment

Aggressive rehydration with n o r m a l saline; diuresis with furosemide to increase sodium a n d c o n c o m i t a n t calcium excretion. Calcitonin, plicamycin, or b i s p h o s p h o n a t es (etidronate, Pamidronate) may b e necessary.

Discussion

Hypercalcemia may occur in hyperparathyroidism, milk-alkali syndrome, multiple myeloma, Addison's disease, sarcoidosis, p r o l o n g e d immobilization, metastatic neoplastic disease ( d u e to increased osteoclastic r e s o r p t i o n ) , a n d p r i m a r y neoplastic disease (due to p r o d u c t i o n of a PTH-like substance). Fifty p e r c e n t of s e r u m calcium is b o u n d to albumin; most of the rest is actively reabsorbed in the proximal tubule t o g e t h e r widi sodium. This reabsorpiion is decreased with expansion of extracellular fluid volume.

ID/CC

HPI PE

Labs

Imaging

A 53-year-old white female goes to her family doctor for a routine physical and is found to be hypercalcémie. She is asymptomatic except for mild polyuria. VS: mild hypertension. PE: no neck masses; thyroid not palpable; no lymphadenopathy; lungs clear; heart sounds normal; abdomen soft; no masses. Increased serum calcium; phosphorus low; elevated PTH; increased alkaline phosphatase. UA: increased urinary calcium; elevated urinary cAMP and hydroxyproline levels. ABGs: hyperchloremic metabolic acidosis (normal anion gap). ECG: short Q-T. XR: subperiosteal bone resorption; cystic long-bone lesions (BROWN TUMORS). NUC: increased bone uptake on bone scan.

Gross Pathology

Soft, round, well-encapsulated, yellowish-brown single parathyroid adenoma weighing 2 g.

Micro Pathology

Chief cells within adenoma.

Treatment

Surgical removal.

Discussion

Primary hypersecretion of parathyroid hormone may be caused by an adenoma (vast majority of cases), chief-cell hyperplasia, or carcinoma of the parathyroid glands; it is commonly asymptomatic and is frequently recognized during routine physical exams. When it is symptomatic, peptic ulcer pain, polyuria, polydipsia, constipation, and pancreatitis may be the presenting symptoms. May be associated with multiple endocrine neoplasia (MEN) syndromes I and II.

Atlas Links

nTcCTTI PM-BC-013, PG-BC-013

HYPERPARATHYROIDISM —PRIMARY

ID/CC

HPI

A 3o-year-old female visits her family doctor because of anxiety, palpitations, intolerance to heat, nervousness with trembling hands, and weight loss despite a normal appetite. She is also concerned about increasing protrusion of her eyes (EXOPHTHALMOS).

PE

VS: tachycardia; hypertension (BP 150/80). PE: wide pulse pressure; sweaty palms; warm skin; exophthalmos (due to enlargement of extraocular muscles); generalized enlargement of thyroid gland with bruit (DIFFUSE GOITER); nodular lesions over anterior aspect of lower legs (PRETIBIAL MYXEDEMA).

Labs

Markedly decreased TSH (due to negative feedback of autonomously secreted thyroid hormones); increased T 3 , T 4 , and free T 4 index; positive TSH receptor antibodies and antinuclear antibodies; hypercalcemia. CBC: anemia.

Imaging

Nuc: increased radioactive iodine uptake measurement; enlarged gland.

Gross Pathology

Increased vascularity of thyroid gland with symmetrical enlargement.

Micro Pathology

Thyroid gland hypertrophy and hyperplasia; reduced thyroid hormone storage and colloid; infiltrative ophthalmopathy.

Treatment

Antithyroid drugs; radioactive iodine.

Discussion

Also called diffuse toxic goiter, Graves' disease is the most common cause of hyperthyroidism. It is idiopathic in nature but has an autoimmune basis and is associated with HLA-B8 and HLA-DR3. LATS, an IgG, is responsible for some manifestations. Signs and symptoms are due to excess circulating thyroid hormone.

Atlas Links

LM< L'U I PM-BC-OK

•

•

MC-090A, MC-090B

HYPERTHYROIDISM (GRAVES' DISEASE)

ID/CC

A 41-year-old obese female comes to the ER with severe epigastric pain radiating to the back accompanied by nausea and vomiting; she had been advised to undergo laparoscopic removal of symptomatic small gallbladder stones.

HPI

She was admitted to the surgical floor and treated for pancreatitis. On the third day, she developed numbness of the fingers and around the mouth and tongue as well as painful leg cramps (i IYPOCALCEMIC TETANY) .

PE

VS: hypotension; tachycardia; fever. PE: dehydrated and in acute distress: bilateral basal hypoventilation; abdomen lender in epimesogastrium; hypocalcémie signs present; abduction and flexion of foot when peroneal nerve is lapped (POsrriVT. PERONEAL SIGN); hyperexcitability while using galvanic current (ERB'S SIGN); facial spasm on tapping over cheek (CHV< »SII K'S SIGN); carpal spasm seen with arterial occlusion by blood pressure cuff (TROUSSEAII'S SIGN).

Labs

Imaging

Gross Pathology

Treatment

CBC: marked leukocytosis (17,000) widi neutrophilia. Amylase and lipase markedly elevated (due to acule pancreatitis). F.( X •: Q-T prolongation. Markedly reduced serum calcium; not nial serum albumin. KUB: increase in gastrocolic space: sentinel loop. CXR: small left pleural effusion. Hemorrhagic pancreatitis with edema and areas of gray-white necrosis; intraperitoneal free hemorrhagic fluid; chalky-white fat necrosis (saponification of calcium with lipids). Treat pancreatitis. IV calcium gluconate.

HYPOCALCEMIA FROM PANCREATITIS

ID/CC

HPI

PE

Labs

A 73-year-old female complains of weakness, painful muscle cramps, and constipation. She suffers from chronic congestive heart failure (CHF) that has been treated with digoxin and furosemide. She was also on oral potassium tablets but has discontinued them because of gasuic upset. VS: irregularly irregular pulse (atrial fibrillation); hypertension (BP 145/90); no fever. PE: well hydrated; conjunctiva normal; jugular venous pulse slightly increased, S3 heard; mild hepatomegaly and pitting edema of lower legs (all due to CHF) ; deep tendon reflexes hypoactive. CBC: normal. Lytes: hypokalemia. ECG; flattening of S-T segment and T waves; prominent U waves.

Treatment

Potassium-rich foods (chick peas, bananas, papaya); oral potassium supplements; gastric mucosal protective agents; magnesium supplements (deficiency of magnesium frequendy coexists). Potassium-sparing diuretics.

Discussion

Potent diuretics such as furosemide frequently cause excessive renal loss of potassium with symptomatic hypokalemia which. if severe, may be life-threatening. In patients on digoxin, hypokalemia greatly increases toxicity.

HYPOKALEMIA

ID/CC

A 48-year-old female who has b e e n o n total parenteral nutrition for 2 weeks complains of weakness, cramps, palpitations, t r e m o r s , a n d depression.

HPI

O n e week ago, she u n d e r w e n t h e r fifth major a b d o m i n al operation for intestinal fistula a n d sepsis.

PE

VS: tachycardia; hypotension. PE: patient looks confused a n d "run down"; agitation with muscular spasticity and hyperreflexia; h e a rt s o u n d s disclose skipped beats; mild hypoaeration at lung bases; a b d o m e n with t h r e e colostomy bags at site of fistula; n o peritoneal irritation; n o surgical w o u n d infection.

Labs

CBC: neutrophilic leukocytosis. Lytes: hypomagnesemi a ( < 0.8 m m o l / L ) ; b o r d e r l i ne hypokalemia; hypocalcemia (severe h y p o m a g n e s e m i a r e d u c e s PTH secretion); low 24-hour urinary magnesium excretion. ECG: p r o l o n g e d P-R a n d Q-T intervals; wide Q R S ; tall T waves; p r e m a t u r e ventricular ectopic contractions.

Treatment

Magnesium s u p p l e m e n t a t i o n. Hypokalemia a n d hypocalcemia resolve with magnesium replacement.

Discussion

Homeostasis of magnesiu m is achieved t h r o u g h a balance between intestinal (small bowel) absorption a n d urinary excretion. Deficiency is associated with the use of a large a m o u n t of IV fluids, alcoholism, intestinal malabsorption or diarrhea, inadequate replacement in parenteral nutrition, kwashiorkor or marasmus, prolonged GI suction, intestinal fistula, renal tubular .it ulosis, .nid use of drugs sut h .is diuretics, cisplatin, inethi >u exate, amphotericin B, Ciclosporine a n d aminoglycosides.

HYPOMAGNESEMIA

ID/CC

A 37-year-old white female complains of nausea, vomiting, and headache on h e r first postoperative day: the charge m u s e found her having a g r a n d mal seizure.

HPI

She had elective surgery for a benign left ovarian cyst. H e r medical history discloses n o previous illness.

PE

VS: n o fever; n o r m a l h e a r t rate. PE: well hydrated; slight confusion and lethargy as well as general weakness; slight increase in JVP; n o bleeding or dehiscence ( o p e n i n g of surgical w o u n d ) or iniection from surgical wound: no peritoneal signs; significant bilateral lower extremity e d e m a .

Labs

CBC: n o r m a l . Lytes: h y p o n a t r e m i a (Na 115). R e m a i n d e r of routine lab exams n o r m a l ; n o r m a l Cortisol ( d o n e to exclude possible a d re n al insufficiency); serum osmolality < 280.

Treatment

For hyper- or isovolemic hyponatremia: water restriction (with caution to avoid osmotic central p o n t i n e myelinolysis syndrome, which can occur while restoring sodium levels t oo quickly). For hypovolemic hyponaü'emia: isotonic saline, slowly.

Discussion

Hyponatremi a is the most c o m m o n electrolyte disturbance seen in hospitalized patienLs a n d is often iatrogenic in n a t u r e . In a postoperative setting, the metabolic response to t r a u m a is to increase secretion of A D H , a m o n g o t h e r h o r m o n e s , which, coupled with overzealous IV administration of hypotonic fluids, may lead to symptomatic hyponatremia.

HYPONATREMIA

ID/CC

HPI

PE

Labs

A 48-year-old obese white female who works as a j a n i t o r is b r o u g h t to t h e ER in a coma after being found on t h e floor of her room. H e r h u s b a n d reveals that she has b e e n having episodes of earlymorning dizziness a n d confusion associated with hunger a n d walking; h e adds that these symptoms di sa p p e ar after eating. H e also states that t h e patient has frequently b e e n nervous and irritable. VS: tachycardia ( H R 105); BP n o r m a l . PE: patient comatose; mild skin pallor; cold, sweaty hands; n o focal neurologic deficits; h e a r t s o u n d s rhythmic; n o m u r m u r s ; lungs clear; abd o m e n soft; n o masses; peristalsis present. Normal h e m o g l o b i n (14.4 m g / d L ) ; BUN a n d creatinine normal. Lytes: n o r m a l . Hypoglycemia (blood glucose 38 m g / d L ) ; elevated insulin; elevated plasma immunoreactive C-peptide (vs. e x o g e n o u s insulin administration, where C-peptide is low). Positive 72 h o u r fasting test (increased insulin levels despite

hypoglycemia). Imaging

CT: 1.5-crn mass in tail o f pancreas. Nuc: mass takes u p octreotide.

Gross Pathology

Single a d e n o m a t o u s mass.

Micro Pathology

Findings according to type of islet cell involved.

Treatment

I m m e d i a te IV glucose infusion; surgical resection

Discussion

T h e most c o m m o n pancreatic islet cell t u m o r is ß-cell insul i n o m a (usually b e n i g n ) . O t h e r types include glucagonomas . s o m a t o s i a l i n o m a s , g a s t r i n o m a s (ZOLLINGER-ELLISON SYNDROME),

a n d excessive VIP-secreting t u m o r (VF.RNER-MORRISON SYNDROME). Islei cell tumors may be seen in multiple e n d o c r i n e neoplasia (MEN) syndromes.

INSULINOMA

o c—I

o

CD

-
350 m O s m / k g ) . Lytes: hypernatremia; mild hypokalemia. Normal anion gap. ABGs: n o r m a l s e r u m bicarbonate (no acidosis). Elevated BUN a n d s e r u m creatinine (suggestive of prerenal azotemia). UA: glycosuria with no ketonuria.

Treatment

Hypotonic (one-half n o r m a l ) saline. Insulin infusion (e.g., lower dose than in ketoacidosis). Potassium a n d p h o s p h a t e supplem e n t as n e e d e d .

Discussion

Hyperosmolar, hyperglycemic nonketotic c o m a occurs mainly in older NIDDM patients a n d is usually associated with an episode of physical or mental stress (check for silent MI); it is not associated with ketosis or ketoacidosis. Volume depletion is severe (average fluid deficit 2 5 % of total body water), a n d the mortality rale is high.

NONKETOTIC HYPEROSMOLAR COMA

ID/CC

A 44-year-old male is admitted to the orthopedic department because he sustained a femoral neck fracture when he fell from a small stool; the type and magnitude of the fracture are not compatible widi the patient's age and impact.

HPI

The patient recently emigrated from Somalia and states that he has been suffering from increasing leg weakness and persistent lower back pain.

PE

VS: normal. PE: complete right femoral neck fracture; on palpation, tenderness of lumbar vertebrae and pelvic rim.

Labs

Imaging

Micro Pathology

Mild anemia (Hb 10 g/dL). Lytes: normal. Increased alkaline phosphatase; decreased levels of 25-OH-D3; hypocalcemia; hypophosphatemia; increased PTH. XR, hip: surgical neck femoral fracture. XR, lumbal- spine: collapse of lumbar vertebrae; generalized osteopenia; pseudofractures (appearance of nondisplaced fractures representing local bone resorption). Excess osteoid but poor mineralization.

Treatment

Vitamin D, calcium (and sometimes phosphate) supplements; surgical treatment of fracture, physiotherapy.

Discussion

A poor diet in vitamin D and calcium, lack of sunlight exposure, intestinal malabsorption, renal insufficiency, or target organ resistance may lead to osteomalacia in the adult (or rickets in children), with defective calcification of osteoid.

OSTEOMALACIA

ID/CC

A 40-year-old male visits his internist for an evaluation of sudden (PAROXYSMAL) attacks of headache, perspiration, and anxiety; attacks are precipitated by exercise, emotional stress, postural changes, and, at times, urination.

HPI

Very high blood pressure has been recorded at the time of previous paroxysms. The patient has a good appetite but looks cachectic; blood pressure recorded between paroxysms is normal. The patient has no history suggestive of renal disease.

PE

Labs

Imaging

VS: hypertension (BP 180/120). PE: hypertensive retinopathy changes on fundtiscopic exam. Elevated blood sugar (due to increased catecholamines). Lytes: normal. Increased 24-hour urinary free catecholamines and vanillylmandeUc acid (VMA) levels. CT/MR: 5-cm left adrenal mass: very high signal on T2-weighted MR. Nuc: MIBG localizes to tumor and metastases.

Gross Pathology

Encapsulated, dusky-colored, round tumor mass with compressed adrenal gland remnants at periphery and foci of necrosis and hemorrhage.

Micro Pathology

Nests of pleomorphic large cells with basophilic cytoplasm and chrome-staining granules in vascular stroma; argentaffin stains positive; membrane-bound secretory granules on electron microscopy.

Treatment

Treat hypertensive crises with pharmacologic alpha and beta blockade (pretreat with alpha blockers prior to beta blockers); resection of tumor.

Discussion

Pheochromocytoma is the most common tumor of the adrenal medulla in adults; ils symptoms are produced by increased production of catecholamines. Of these tumors, 10% are extraadrenal, 10% bilateral, 10% malignant, and 10% familial; 10% occur in children, and 10% calcify. May be associated with multiple endocrine neoplasia (MEN) IIA or IIB syndromes.

Atlas Links

ETCBÜJ PM-BC-026, PG-BC-026A, PG-BC-026B

PHEOCHROMOCYTOMA

ID/CC

A 9-year-old female is b r o u g h t to h e r pediatrician because of breast enlargement.

HPI

H e r m o t h e r also reports cyclical vaginal bleeding a n d the app e a r a n c e of pubic and axillary hair since the age of 4; an older cousin developed similar signs a n d symptoms.

PE

Fully developed breasts; axillary a n d pubic hair present; normal mental development ; height a n d weight greater than average lor h e r age; n o focal neurologic signs.

Labs

Imaging

Gross Pathology

Increased plasma FSH, LH. a n d estradiol; pubertal pattern of increased g o n a d o t r o p i n s after infusion of G n R H . XR: advanced bone age. US: ovary enlarge d to pubertal size with cyst formation. C T / M R : n o pituitary lesion. Ovarian cyst formation (luteal): in idiopathic variety, n o structural abnormality found.

Treatment

G n R H agonists; psychiatric support; c o n t i n u o u s search for possible cause.

Discussion

T h e most c o m m o n cause of precocious puberty is idiopathic or constitutional; less c o m m o n causes include hypothalamicpituitary tumors (pinealomas, h a m a r t o m a s , gliomas) or lesions causing g o n a d o t r o p i n - d e p e n d e n l precocious puberty.

PRECOCIOUS PUBERTY

ID/CC

HPI

PE

A 5-year-old boy is brought to the pediatrician because of intermittent numbness and leg cramps. His father is also concerned about the fact that his child is shorter than his classmates. Full, round face; short neck; flat nasal bridge; right convergence squint and left cataract; delayed dentition; positive Chvostek's anil Trousseau's signs.

Labs

CBC: normal. Lytes: hypocalcemia ( < 8.8 mg/dL); hyperphosphatemia (> 5 mg/dL). Increased plasma PTH; no increase in renal cAMP and phosphate clearance with PTH infusion.

Imaging

XR: fourth and fifth metacarpals are short; premature physeal closure; thickening of cortices with demineralization.

Treatment

Calcitriol and calcium supplementation.

Discussion

Also called Seahright-Bantam syndrome, pseudohypoparathyroidism is an X-linked dominant disorder in which there is resistance to PTH action on the renal tubule and bone with resulting hypocalcemia. Two types exist according to the response of cAMP to PTH. In type I (as in this case), patients fail to exhibit a Phosphaturie response or increased cAMP after administration of PTH. Type II is associated with Albright's hereditary osteodystrophy.

PSEUDOHYPOPARATHYROIDISM

ID/CC

A 15-month-old Eskimo boy is brought to the pediatric clinic by his parents because of delayed dentition, poor growth and development, frequent crying, and weakness.

HPI

The infant's diet is deficient in eggs and dairy products, and he spends most of his time indoors (i.e., he has no exposure to sunlight).

PE

Irritability; poor muscular development and muscle tone; abdominal distention; hypotonia of all muscles; anterior fontanelle open ; softening of occipital and parietal bones with elastic recoil (CRANIOTABES); frontal bossing; enlargement of costochondral junctions (RACHITIC ROSARY); bowing of legs; lineal chest depression along diaphragm (HARRISON'S GROOVE).

Labs

Imaging

Serum calcium normal or slightly low; decreased serum phosphorus; increased alkaline phosphatase; low 1,25(OH)^vitamin D level. XR: widening of growth plates: osteopenia of cranial and long bones; irregularity and cupping of distal ends of long bones; pseudofractures in melaphysis (LOOSER'S LINES).

Gross Pathology

Excess amount of uncalcined bone at junction of cartilage; bone stretched and pulled out of shape by gravity; increased osteoid seams; osteopenia; frontal bossing of skull; pigeon breast deformity.

Micro Pathology

Defective mineralization oí osteoid in epiphysis and diaphysis.

Treatment

Increase calcium and vitamin D in diet.

Discussion

Rickets is a disease of infancy and childhood involving defective mineralization of osteoid in bone skeleton and the neuromuscular- system because of low vitamin D or calcium in the diet; it can also be due to low sunlight exposure (vitamin D conversion in skin) and chronic renal failure (BUN and phosphorus levels are high).

ID/CC

HPI

A 61-year-old male smoker presents with headache, weakness. fatigue, and decreased urinary output (oLKil'RlA). He was recently diagnosed with oat cell carcinoma of the lung.

PE

Cardiac sounds normal; no murmurs; no arrhythmias; no pitting edema; no hepatomegaly; no jugular plethora (no evidence of cardiac disease); no asterixis, jaundice, spider nevi, or parotid enlargement (no evidence of hepatic disease).

Labs

Decreased serum sodium (HYPONATREMIA); decreased serum osmolality ( < 280 mOsm/kg); normal or low BUN and serum creaiinine; no proteinuria (no renal disease); adrenal and thyroid function tests normal. UA: urine osmolality markedly increased (versus psychogenic polydipsia where osmolality is decreased); hvpernatriuria (urinary Na > 20 mEq/L). Diminished blood uric acid level (HYPOURICEMIA).

Treatment

Water restriction plus a high-salt diet Demeclocycline.

Discussion

Syndrome of inappropriate (increased) secretion of antidiuretic hormone (SIADH) occurs with either increased hypothalamic secretion (e.g., CNS disease, postoperative states) or ectopic secretion (e.g., tumors such as oat cell carcinoma of the lung). There may also be increased sensitivity to die effect of ADH (as occurs with chlorpropamide, fluoxetine, and carbama/epine).

SIADH

ID/CC

HPI

PE

A 29-year-old female is b r o u g h t by a m b u l a n c e to the emergency r o o m from h e r workplace owing to confusion, agitation, diarrhea, a n d vomiting. H e r sister has myasthenia gravis. She gives a history of recent weight loss (7 kg) a n d a recent severe URI. VS: fever (39.3°C); tachycardia with irregular pulse; hypotension (BP 1 0 0 / 5 0 ) . PE: irritability; delirium; e x o p h t h a l m o s ; diffuse increase in size of thyroid gland (GOITER); lungs clear; a b d o m e n soft a n d n o n t e n d e r ; n o masses; n o peritoneal irritation; d e e p t e n d o n reflexes brisk; n o neck stiffness or focal neurologic signs.

Labs

CBC/Lytes: n o r m a l . LP: CSF values n o r m a l . ECG: atrial filn illation. Elevated T4, free T 4 , a n d T 3 ; low TSH.

Treatment

T r e a t m e n t involves inhibition of thyroid h o r m o n e synthesis (with propyl!hiouracil or m e t h i m a / o l e ) ; inhibition of stored thyroid h o r m o n e (with iodide a n d corticosteroids); suppression of die peripheral effects of thyroid h o r m o n e (with p r o p r a n o l o l ) ; d i g i t i z a t i o n of patients with C H F a n d atrial fibrillation; a c e t a m i n o p h e n for fever; a n d treatmen t of precipitating factors (e.g., antibiotics for infections).

Discussion

Thyroid storm, a medical emergency, is usually precipitated by surgical or medical su*ess (e.g., infection) placed o n u n t r e a t e d or u u d e r t r e a t e d hyperthyroid patients. Prevention of postoperative crises is effected t h r o u g h use of iodine and antithyroid drugs.

THYROID STORM

ID/CC

HPI

PE

A 27-year-old Cuban political dissident visits a medical clinic complaining of diminished visual acuity, primarily at night. He recendy arrived in the United States by boat after spending several years in prison. VS: normal. PE: conjunctiva shows diminished tear lubrication with dryness (XEROSIS; when localized, it forms patches known as Bitot's spots) as well as keratinization and small corneal ulcers (XEROPHTHALMIA).

Micro Pathology

Keratinizing metaplasia in conjunctiva; follicular hyperkeratosis with glandular plugging.

Treatment

Vitamin A supplementation.

Discussion

Vitamin A (RETINOL) is a fat-soluble vitamin derived from ß-carotenes diat is used for the synthesis of rhodopsin in the retina, for wound healing, and for epithelial cell growth and differentiation. Night blindness (NYCTALOPIA) is an early symptom of vitamin A deficiency; conjunctiva] xerosis and Bitot's spots are early signs. Corneal ulcers may progress to erosions and eventual destruction of cornea (KERATOMALACIA).

VITAMIN A DEFICIENCY

ID/CC

HPI

PE

Labs

Imaging

A 36-year-old black male who is known to be an alcoholic comes to the e m e r g e n cy r o o m with shortness of breath , confusion, foot drop, a n d swelling of his legs. He admits to getting d r u n k at least t h r e e times a week. His diet consists mainly of c a n n e d soup a n d c h e a p "junk food" that he eats d u r i n g the periods in which h e is not d r u n k . VS: tachycardia. PE: dyspnea; j u g u l a r venous distention; extremities warm to touch; cardiomegaly; hepatomegaly; 2 + pitting e d e m a of both lower extremities; confusion with nystagmus; decreased d e e p t e n d o n reflexes. Increased RBC transketolase activity coefficient; low serum a n d u r i n e t h i a m i n e levels. CXR: cardiomegaly with basal lung congestion.

Gross Pathology

Wernicke's e n c e p h a l o p a t h y shows congestion, h e m o r r h a g e s , a n d necrosis in thalamus, h y p o t h a l a m us (manunillary bodies), and paraventricular regions.

Micro Pathology

Demyelinizatíon of pe ri p h e ral nerves with axonal d e g e n e r a t i o n and Itagineniation.

Treatment

Thiamine. Before administering glucose to an alcoholic, thia m i n e should be given to prevent e n c e p h a l o p a d i y (due to depletion of thiamine in glycolysis pathways). Alcoholics should also receive PV or oral folate a n d multivitamins.

Discussion

Lack of thiamine p r o d u c e s Wernicke-Korsakoff sy n d r o me as well as high-output heart failure (wet beriberi) and polyneuropathy (dry beriberi). T h i a m i n e p y r o p h o s p h a t e (TPP) is a cofactor for the Krebs cycle enzymes a-ketoglutarale d e h y d r o g e n a se a n d pyruvate d e h y d r o g e n a s e as well as transketolase (pentose phosp h a t e pathway).

VITAMIN Bj DEFICIENCY (BERIBERI)

ID/CC

A 45-year-old alcoholic Hispanic male who recently underwent a strangulated hernia repair becomes irritable and weak, suffers significant weight loss, and develops a rash on his face, his neck, and the dorsum of his hands; he also suffers from diarrhea and altered mental status.

HPI

After his operation (which involved a 5-cm small bowel resection), the patient became torpid and anorexic with lack of proper return of bowel function for about 3 weeks. His diet had been based on corn products.

PE

Labs Micro Pathology

Erythematous, nonpruritic, hypcrpigmented, scaling rash of face, neck (C\SAL's NECKLACE), and dorsum of hands; angular stomatitis (CHEILOSIS) and glossitis; diminished touch and pain sensation in all four extremities; apathy, confusion, and disorientation. UA: low levels of urinary N-methylnicotinamide. Atrophy and ulceration of gastric and intestinal mucosa; posterior columns show neuronal degeneration and demyelination.

Treatment

Oral nicotinamide.

Discussion

Vitamin B^ (NIACIN) deficiency (PELLAGRA) is commonly seen in alcoholics and is less frequently seen in patients with GI disorders or in elderly patients. In patients widi carcinoid syndrome, tryptophan, the precursor of niacin, is used up to form serotonin. It is usually accompanied by other B vitamin deficiencies. The typical observed triad consists of dermatitis, dementia, and diarrhea.

VITAMIN B3 DEFICIENCY (PELLAGRA)

ID/CC

HPI

A 9-month-old white female is brough t to the pediatric clinic because of list lessness and anorexia. She is the d a u g h t e r of an u n e m p l o y ed poor urban couple a n d has never before seen a pediatrician or taken any medication. H e r parents r e p o r t a diet of unsupplemented cow's milk.

PE

Weakness; pallor; hyperkeratosis a n d hemorrhagic perifolliculitis of skin of lower extremities, forearms, a n d a b d o m e n ; purpuric skin rashes; splinter hemorrhages in nail beds of hands; t e n d e r n e ss a n d swelling of distal femur a n d costochondral j u n c t i o n s ; bleeding gums; petechiae seen over nasal and oral nuit osa.

Labs

CBC: microcytic, hypochromic anemia; leukopenia. Plasma a n d platelet levels of ascorbic acid low; prolonged bleeding time.

Imaging

Gross Pathology

XR: subperiosteal h e m o r r h a g e s ; both legs a n d knees show "ground glass" a p p e a r a n c e of bones a n d epiphyses, Growing b o n e shows diminished osteoid formation, h e m a r t h r o sis, a n d subperiosteal a n d periarticular h e m o r r h a g e : defective collagen (vitamin C hydroxylates proline a n d lysine); e n d o c h o n dral b o n e formation ceases (osteoblasts fail to form osteoid) ; existing trabeculae brittle a n d susceptible to fracture.

Treatment

©ral ascorbic acid (high doses may p r o d u c e oxalate a n d uric acid stones).

Discussion

Vitamin C (ASCORBIC ACID) deficiency, o r scurvy, is observed in smokers, oncologic patients, alcoholics, infants, a n d the elderly.

VITAMIN C DEFICIENCY (SCURVY)

ID/CC

HPI

PE

Labs

A 47-year-old homeless alcoholic m a n (with a diet deficient in leafy- vegetables) comes into the e m e r g e n cy r o o m widi weakness, bleeding gums, swelling in his right k n e e d u e to blood collection (HEMARTHROSIS). a n d bloody vomit (HEMATEMESIS). The patient's diet consists of o n e meal a day of leftovers from fast-food restaurants. H e was given ampicillin for d i a r r h e a 2 weeks ago (leading to suppression of vitamin K synthesis by colonic bacteria). Thin a n d malnourished with p o o r hygiene; conjunctival a n d nail bed pallor; subcutaneous ecchymosis in a r m s a n d legs; right k n e e hemarthrosis. Anemia ( H b 9.7); prolonged PT and PTT; n o r m a l platelet count, fibrinogen level, and t h r o m b i n time.

Treatment

Vitamin K s u p p l e m e n t a t i o n .

Discussion

Coagulation factors II, VII, IX, a n d X are d e p e n d e n t o n vitamin K f o r their activity ( d i r o u g h y-carboxylation). Broad-spectrum antibiotic use, malabsorption, a n d lack of dietary vitamin K result in deficiency, manifested as bleeding. Since these factors are m a d e by the liver, severe liver disease can cause coagulopathy.

VITAMIN K DEFICIENCY

ID/CC

A 47-year-old male high-school t e a c her visits his internist hecause of chronic watery diarrhea a n d hot flashes while drinking alcohol; a few m o n t h s ago h e also noticed a peculiar r e d n e s s of his face.

HPI

Every time h e works o r exercises in the sun, h e develops a rash on exposed areas (PHOTODERMATITIS).

PE

VS: n o r m a l . PE: in n o acute distress; r e d n e s s of face; n o neck masses or increased JVP; systolic ejection m u r m u r grade I/TV at p u l m o n a r y area, increasing with inspiration ( p u l m o n a r y stenosis); wheezing heard; a b d o m e n soft a n d n o n t e n d e r ; mild hepatomegaly.

Labs

Imaging

CBC/Lytes: n o r m a l. Glucose, BUN, creatinine, a n d LFTs n o r m a l ; n o ova or parasites in stool. L'A: increased 5hydroxyindoleacetic acid (5-HIAA) in u r i n e (a p r o d u c t of serotonin d e g r a d a t i o n ) . KUB: ladder-step air-fluid levels. UGI: small bowel loops kinked, causing obstruction. CT: starlike thickening of mesentery d u e to desmoplastic retraction; vague liver metastatic lesions.

Gross Pathology

Firm, yellow, submucosal n o d u l e in a s e g m e nt of ileum.

Micro Pathology

Argentophilic cells (KULCHITSKY CELLS) in the intestinal crypts of L i e b e r k ü h n invading into mesentery; m a r k e d fibrotic reaction.

Treatment

O c t r e o t i d e , c y p r o h e p t a d i n e (SOMATOSTATIN VNALOG).

Discussion

Carcinoid tumors arise from the gastrointestinal tract or bronchi. These t u m o r s secrete serotonin (D-HYDROXYTRYPTAMINE), producing the typical clinical syndrome. T h e r e may be stenosis of the p u l m o n i c a n d tricuspid valve a n d right-sided hear t failure.

CARCINOID SYNDROME

ID/CC

A 3-week-old male is seen by a neonatologist because of severe jaundice that appeared at birth and has been worsening ever since.

HPI

He is the first-born child of a healthy Jewish couple. His mother had an uneventful pregnancy and delivery.

PE

Average weight and height for age; in no acute distress; marked jaundice (jaundice appears at levels of bilirubin around 2.5 to 3.0 mg/dL); slight hepatomegaly.

Labs

Markedly increased serum unconjugated bilirubin ( 15 mg/dL) ; very low fecal urobilinogen.

Treatment

Phénobarbital for type II. For type I, the prognosis is guarded, with the likelihood of death in the first year of life.

Discussion

Crigler—Najjar syndrome is an inherited disorder of bilirubin metabolism that is characterized by a deficiency of the enzyme glucuronyl transferase and hence by an inability to conjugate bilirubin, with accumulation of indirect bilirubin and risk of kernicterus with brain damage (at bilirubin concentrations of > 20 mg/dL). There are two types: type I, which is more severe and is autosomal recessive, and type II, which is autosomal dominant.

CRIGLER-NAJJAR SYNDROME

ID/CC

A 21-year-old female college student visits her gastroenterologist for an evaluation of fatigability and intermittent right upper quadrant and epigastric pain.

HPI

She asked her family doctor to refer her lo a gastroenterologist because she was concerned about her pain despite her doctor's reassurance that it was "nothing important."

PE

VS: normal. PE: mild jaundice in conjunctiva and underneath tongue; well hydrated and in no acute distress; no hepatosplenomegaly on abdominal exam; no signs of hepatic failure.

Labs

Increased direct bilirubin (vs. Gilbert's syndrome, in which hyperbilirubinemia is indirect) and indirect bilirubin; liver enzymes mildly elevated. UA: bilirubin and urobilinogen (vs. Gilbert's syndrome); ratio of coproporphyrin I and coproporphyrin LTI in urine 5:1 (normal = 1).

Imaging

US: no gallstones; liver normal. Nuc: no biliary excretion on HIDA.

Gross Pathology

Liver normal size and dark green in color (versus Rotor syndrome, which has no gross liver abnormalities); absence of gallbladder inflammation or stones.

Micro Pathology

Centrilobular, lysosomal granules with brownish pigment (catecholamines).

Treatment

Supportive.

Discussion

Dubin-Johnson syndrome is a benign autosomal-recessive disorder (vs. Gilbert's syndrome) of defective canalicular bilirubin excretion characterized by episodes of intermittent jaundice.

DUBIN-JOHNSON SYNDROME

ID/CC

HPI

A 19-year-old male with a URI visits his family d o c t or because h e is c o n c e r n e d a b o u t yellowness in his eyes (JAUNDICB), which he luis noticed whenever he is fatigued Ol is suffering Imin a m i n o r infection. H e has n o history of dark-colored u r i n e, clay-colored stools, a b d o m i n a l pain, blood transfusions, or d r u g use. H e is i m m u n i z e d against hepatitis B a n d d o e s not drink alcohol.

PE

Normal except for mild scleral icterus; n o hepatosplenomegaly; n o signs of chronic liver failure.

Labs

Moderately increased serum bilirubin, predominantly unconjugated; normal s e r u m transaminases a n d alkaline phosphatase; n o r m a l s e r u m albumin; serum bilirubin rises after 24-hour fast.

Treatment

No metabolic t r e a t m e n t available or necessary.

Discussion

T h e most c o m m o n e x a m p le of idiopathic hyperbilirubinemia is Gilbert's disease, which is autosomal d o m i n a n t widi variable p e n e t r a n c e . It is d u e to defective bilirubin uptake by liver cells a n d low glucuronyl transferase activity. Bilirubin levels seldom exceed 5 m g / d L , mainly unconjugated, a n d may vary inversely with caloric intake.

GILBERT'S DISEASE

ID/CC

A 19-year-old female is b r o u g h t to h e r family d o c t o r by h e r parents, who have noticed that she has started behaving oddly; 2 days ago they noticed that her eyes were yellow.

HPI

She also complains of t r e m o r of h e r h a n d s at rest a n d some rigidity when trying to grasp objects (basal ganglia affectation). T h e p a r e n t s of the patient are first cousins.

PE

Patient shows flapping t r e m o r (ASTERLXJS) of h a n d s ; slit-lamp examination reveals c o p p e r deposits in Descemet's m e m b r a n e of the c o r n e a (KAYSER-FLEISCHER RINGS); a b d o m i n a l palpation shows m o d e r a t e splenomegaly.

Labs

CBC: hemolytic a n e m ia (due to oxidative RBC d a m a g e by copper). AST a n d ALT elevated as well as alkaline p h o s p h a t a se a n d bilirubin, both direct a n d indirect; decrease in s e r u m ceruloplasmin (copper-transporting p r o t e i n ) ; increased urinary c o p p e r (IIYI'ERCI'I'RIIRIA): increased urinary uric acid (HYPERURICOSURIA).

Imaging

US: e n l a r g e m e n t of liver a n d spleen.

Gross Pathology

C o p p e r accumulation in liver, brain, a n d c o r n e a .

Micro Pathology

Liver biopsy shows acute inflammation, increased c o p p e r levels, a n d periportal fibrosis ( m a c r o n o d u l a r cirrhosis); intracytoplasmic hyaline bodies (MALLORY BODIES) seen: degeneration of basal ganglia with cavitation, especially of p u t a m e n ; hyperplasia with glial proliferation of the lenticular nuclei.

Treatment

Penicillamine (coppe r chelating d r u g ) , pyridoxine. Conside r liver transplantation.

Discussion

Wilson's disease is an autosomal-recessive inherited disorder of c o p p e r metabolism m a p p e d to c h r o m o s o m e 13. It is characterized by increased absorption of c o p p e r from the intestine a n d diminished excretion in the bile with resultant c o p p e r deposition, primarily in the brain a n d liver.

WILSON'S DISEASE

ID/CC

A 23-year-old white female is b r o u g h t to the ER because of strange, dreamlike hallucinations and blurred vision that she e x p e r i e n c e d 1 day after spending all morning in the sun painting h e r h o u s e (exposure to sun may precipitate attacks).

HPI

T h e patient had u n d e r g o n e two previous laparotomies for app a r e n t acute a b d o m e n , but no pathology was found. She has had several episodes of recurrent abdominal pain.

PE

VS: n o fever or tachycardia. PE: pupils are of u n e q u a l size (ANISOCORIA); generalized weakness a n d hypoactive d e e p - t e n d o n reflexes; disorientation; foot drop; urine very dark a n d foulsmelling. No photosensitive skin lesions.

Labs

UA: increased urine porphobilinogen a n d y-aminolevulinic acid. Lytes: hyponatremia.

Gross Pathology

Liver infiltrated with p o r p h o b i l i n o g e n ; cenUal a n d p e r i p h e r al n e r v o u s system myelin sheath d e g e n e r a t i o n .

Micro Pathology

Degeneratio n of myelin sheath.

Treatment

High-carbohydrate diet; glucose; h e m a t i n .

Discussion

Acute intermittent porphyria is an autosomal-dominant deficiency in an enzyme of porphyrin metabolism (porphobilinogen deaminase) that leads to systemic symptoms, acute a b d o m i n a l pain, neuropsychiatrie signs a n d symptoms, a n d CNS a n d peripheral neuropathy. Acute intermittent porphyria is differentiated from o t h e r porphyrias by ils lack of photosensitive skin lesions. Sun exposure a n d d r u g s (e.g., sulfa, barbiturates) may precipitate attacks.

ACUTE INTERMITTENT PORPHYRIA

ID/CC

A 27-year-old farmer from Florida (with abundant sun exposure) comes to see his dermatologist for an evaluation of a recent increase in size and change in color of a skin lesion that has been present on the dorsum of his hand (a sun-exposed area) for 6 years.

HPI

The patient is an albino, but he has not been able to comply with his dermatologist's orders to wear long sleeves while working in the field.

PE

White hair, including eyelashes and eyebrows; eye exam shows nystagmus and poor development of macula with blue iris; poor visual acuity (20/350); skin is pink-white with lack of pigmentation throughout body; numerous actinic (SOLAR) keratoses on face and scalp as well as on dorsum of hands; ulcerated lesion with indurated edges on dorsum of hand with hyperpigmentation.

Labs

Tyrosine assay shows absence of the enzyme.

Gross Pathology

Patches of scaly, irregular, hypertrophied skin in sun-exposed areas (actinic keratosis).

Micro Pathology

Biopsy of lesion on dorsum of hand shows epidermoid (squamous cell) cancer with epithelial pearls.

Treatment

Surgery a n d / o r chemotherapy for skin cancers, avoidance of sun exposure, management of visual impairment

Discussion

Albinism is a hereditary disorder that may be generalized or localized and is transmitted as an autosomal-dominant or autosomal-recessive trait. Il is always distinguished by various degrees of hypopigmentation of the skin, hair, iris, and retina. The defect lies in the pigmentation, not in the number of melanocytes present in the body. The cause is an absence of tyrosinase, the enzyme that catalyzes the conversion of tyrosine to dihydroxyphenyialanme and melanin. There is a marked increase in the risk of skin cancer.

JJ ALBINISM

ID/CC

HPI

PE

Labs

Imaging

A 37-year-old man presents with dark, blackened spots in his sclera and ear cartilage as well as back pain and restriction of motion with pain and swelling of both knee joints. Directed questioning reveals that his urine turns black if left standing. Increased pigmentation in ears, conjunctiva, nasal bridge, neck, and anterior thorax (OCHRONOSIS); arthritis of spine, both knee joints, and fingers. UA: elevated urine homogentisic acid (causes urine to darken upon standing or with addition of alkaline substances). XR: calcification in cartilage of knee menisci and wrist; premature arthritic changes.

Treatment

Symptomatic treatment of arthritis.

Discussion

Also called ochronosis, alkaptonuria is an autosomal-recessive disorder of tyrosine metabolism characterized by the absence of homogentisate oxidase due to a defective gene on chromosome 3 with accumulation of homogentisic acid in cartilage, giving a dark blue discoloration to the tissues and leading to degenerative joint disease.

ALKAPTONURIA

ID/CC

An 11-year-old white female is b r o u g h t to the ER by her parent s because of fever, difficulty breathing, and a productive cough with greenish sputum.

HPI

H e r p a r e n t s are of n o r t h e r n E u r o p e a n descent. She has a history of recurrent UTIs and foul-smelling diarrhea since infancy.

PE

VS: tachycardia; tachypnea (RR 45). PE: mild cyanosis; malnourislmient: nasal polyps; h y p e r r e s o n a n c e to lung percussion with barrel-shaped chest; scattered rales; hepatomegaly.

Labs

High sodium and chloride concentrations in sweat test; Pseudomonas aeruginosa. Haemophilus influenzae and Staphylococcus aureus in s p u t u m culture. PFTs: increased R V / T L C ratio. Increased fecal fat. ABGs: hypoxemia; hypercapnia.

Imaging

CXR: few dilated bronchi (BRONCHIECTASIS) filled with mucus; e m p h y s e m a ; XR, paranasal sinuses: opacification of sinuses.

Gross Pathology

Atrophic pancreas with almost c o m p l e t e disruption of acini a n d r e p l a c e m e n t of exocrine pancreas with fibrous tissue a n d fat; m u c o u s plugging of canaliculi.

Micro Pathology

Inflammatory c h a n g e .

Treatment

Antibiotics, low-fat diet, a n d supportive measures; r e c o m b i n a n t h u m a n DNase (cleaves extracellular DNA from n e u t r o p h i l s in sputum); inhaled amiloride, nasal corticosteroids, systemic corticosteroids, decongestants; consider lung t r a n s p l a n t

Discussion

Cystic fibrosis is an autosomal-recessive disease that is d u e to a mutation in the long a r m of chromosome 7 (band q31) in the cystic fibrosis t r a n s m e m b r a n e c o n d u c t a n c e regulator (CFTR) g e n e . If CFTR function is deficient, chloride a n d water transport is slowed and secretions are inspissated.

CYSTIC FIBROSIS

ID/CC

HPI

A 15-year-old female is b r o u g h t to t h e e m e r g e n c y r o o m from school following the s u d d e n d e v e l o p m e n t of severe, intermittent right-flank pain t o g e t h e r with nausea, vomiting, a n d blood in her urine (a picture typical of r e n o u r e t e r a l s t o n e ). H e r medical a n d family history is u n r e m a r k a b l e .

PE

VS: tachycardia; n o r m a l BP; slight fever. PE: short stature (due to lysine deficiency); in acute distress; constantly switches positions in b e d ( d u e to renal colic); abdominal tenderness; n o peritonea] irritation; costovertebral angle t e n d e r n e s s.

Labs

Increased urinary excretion of cysteine, ornithine, arginine, and lysine on urine a m i n o acid chromatography (due to intestinal a n d renal defect in reabsorption). UA: hematuria; hexagonal crystals (CYSTEINE) u p o n cooling of acidified u r i n e sediment.

Imaging

K U B / I V P / C T urography: r a d i o p a q u e stone in area of right kidney.

Treatment

Low-methionine diet; increase fluid intake; alkalinize urine; penicillamine.

Discussion

Cystinuria is an autosomal-recessive disorder of dibasic a m i n o acid metabolism ( d u e to impaired renal tubular r e a b s o r p t i o n ) ; it leads to increased cysteine urinary excretion a n d kidney stone formation.

CYSTINURIA

ID/CC

A 9-year-old boy is brought to the emergency room with pain, inability to move his left shoulder, and flattening of the normal rounded shoulder contour (SHOULDER DISLOCATION) that Occurred when he tried to hit a ball with his bat at a local baseball field.

HPI

He lias dislocated his left shoulder nine times before and his right shoulder three times before. He also has a history of easy bruising.

PE

Labs Imaging Micro Pathology

Hyperelastic skin; "cigarette paper" scars in areas of trauma; hyperextensibility of joints; left shoulder dislocated; multiple bruises over skin. Clotting profile normal. XR: left shoulder dislocated. Collagen fibrils of dermis of skin larger than normal and irregular in oudine on electron microscopy.

Treatment

Supportive.

Discussion

Ehlers-Danlos syndrome is also known as cutis hyperelastica. Faulty collagen synthesis produces 10 types of Ehlers-Danlos syndrome, some of which are autosomal recessive (type VI), others autosomal dominant (type IV), and others associated with X-linked recessive transmission (type IX). Prone to aneurysm and dissection in the great vessels.

EHLERS-DANLOS SYNDROME

ID/CC

HPI PE

Labs

Micro Pathology

A 17-year-old male presents with episodes of painful, b u r n i n g paresthesias along his palms and soles along with markedly diminished vision in his right eye. His maternal uncle died of chronic renal failure at the age of 40. ( l u s t e r s of purplish-red, hyperkeratotic lesions on skin a r o u n d umbilicus, buttocks, a n d scrotum (ANGIOKERATOMAS); right corneal l e u k o m a t o us opacity; neurologic exam n o r m a l except for painful paresthesias along a r m s a n d soles; pitting e d e m a in lower extremities. Elevated s e r u m creatinine and B U N (patients usually die of renal failure). UA: proteinuria; b r o a d casts. PBS: leukocytes reveal deficiency of a-galactosidase. Lipid deposition in epithelial a n d endothelial cells of glomeruli a n d tubules (FOAM CELLS) o n renal biopsy; lysosomal accumulation of glycosphingolipid (ceramide trihexoside ) in the form of "myelin bodies" o n electron microscopy of skin, heart, kidneys, a n d CNS.

Treatment

Treat pain crises symptomatically; renal failure may r e q u i r e renal transplantation.

Discussion

Fabry's disease, a sphingolipidosis, is a rare X-linked recessive d i s o r d e r of glycosphingolipid metabolism caused by a deficiency of a-galactosidase A a n d by the c o n s e q u e nt accumulation of c e r a m i d e trihexoside.

FABRY'S DISEASE

ID/CC

HPI

PE

Labs

Imaging

A 28 year-old white male complains of severe retrosternal pain radiating to his left a r m a n d jaw. He has not h a d a physical exam in a long time. H e adds that his father died at a young age of a myocardial infarction. Anguished, dyspneic, diaphoretic male with h a n d clutched to chest (indirect sign of myocardial p a i n ) ; soft, elevated plaques on eyelids (XANTHELASMAS); arcus senilis; painful xanthomas of Achilles tendons and patellae. Elevated CK-MB; elevated t r o p o n i n T a n d I. ECG: MI. Extremely high levels of LDL. Angio: c o r o n a r y artery disease.

Gross Pathology

Premature atherosclerosis in large arteries.

Micro Pathology

Foam cells with lipid characteristic of atherosclerotic plaques.

Treatment

Diet, exercise and cholesterol-lowering drugs (althought HMGCoA reductase inhibitors are ineffective in homozygous FH patients dm to complete lack of LDL receptors) . Consider pot tocaval anastamosis or liver transplantation.

Discussion

Familial hypercholesterolemia is also called type II hyperlipoproteinemia: it is an autosomal-dominant defect in LDL receptor with a g e n e frequency of 1:500. Homozygotes may have an LDL count eight times that of n o r m a l .

FAMILIAL HYPERCHOLESTEROLEMIA

ID/CC

HPI

A 16-year-old white female complains of s u d d e n midepigastric pain and nausea after eating french fries. H e r history reveals that she and a sibling have h a d similar episodes of a b d o m i n al pain in the past. Careful questionin g discloses that she experiences flushing every time she drinks alcohol.

PE

Nonpainful, yellowish papules on face, scalp, elbows, knees, and buttocks (ERUPTIVE XANTHOMATOSIS); lipemia retinàlis on funduscopic exam; hepatosplenomegaly; a b d o m i n a l muscle g u a r d i n g a n d palpable tenderness .

Labs

Elevated serum amylase a n d lipase; very high triglycerides; mod erate elevation of serum cholesterol a n d phospholipids .

Micro Pathology

Lipid-laden foam cells.

Treatment

Low-fat diet; avoidance of alcohol; exercise; fibric acid a n d niacin in selected cases.

Discussion

Familial hypertriglyceridemia is an autosomal-dominan t disorder. Abdominal pain stems from recurrent acute pancreatitis.

FAMILIAL HYPERTRIGLYCERIDEMIA

ID/CC

HPI

An 8-year-old boy is referred to the pediauic clinic for evaluation of anemia and multiple developmental anomalies. His parents report that he bleeds easily.

PE

Pale and mentally retarded; small head (MICROCEPHALIA); low height and weight for age; hyperpigmentation of torso and thighs widi café-au-lait spots; decrease in size of penis; decrease in size of eyes (MICROPHTHALMIA); absence of both thumbs.

Labs

CBC: decreased WBCs (LEUKOPENIA), platelets (THROMBOCYTOPENIA), and RBCs (ANEML o

r— O CD


25%). ABGs: metabolic acidosis.

Imaging

CT/MR: bilateral globus pallidus lesions.

Treatment

One hundred percent oxygen, assisted ventilation if necessary. Hyperbaric oxygen chamber.

Discussion

Common sources of CO are car exhaust, pipes, and fires. Carbon monoxide has a much greater affinity for hemoglobin than oxygen (250 times more). If patient is pregnant, damage to the fetus is devastating (HbF has greater affinity to CO dian HbA). Long-term side effects such as memory problems, lack of coordination, and even convulsions are common after intoxication.

CARBON MONOXIDE POISONING

ID/CC

HPI

PE

Labs

Imaging

A 52-year-old obese white male c o m e s to his family d o c t or complaining of severe pain in the first metatarsophalangeal (MTP) joint (PODAGRA) that began at night after an episode of binge eating and drinking. H e admits to being an avid meat eater a n d drinks red wine every night. His history is significant for removal of kidney stones (uric acid stones). VS: fever (38.2°C). PE: right MTP joint red, hot, a n d swollen; painful to active a n d passive motion; tophaceous deposits in left ear a n d o l e c r a n o n bursitis. Elevated serum uric acid. UA: u r a t e crystals. Increased ESR. CBC: leukocytosis with neutrophilia. XR: p u n c h e d - o u t erosions in right big toe at MTP joint, p r o d u c ing "o v e rh a n g i n g " spicules.

Gross Pathology

Tophi are white, soft, n o d u l a r masses of urate deposits with calcifications seen mainly in synovial m e m b r a n e s , t e n d o n sheaths, a n d ear cartilages.

Micro Pathology

Tophi a n d synovial fluid aspiration show characteristic negatively biréfringent, needle-shaped crystals of uric acid salts; giant tell lot niatioti with neutrophili c infiltration.

Treatment

Colchicine for acute stage; administer hourly until negatively d i a r r h e a occurs o r pain disappears; c o m b i n e with aspirin or \ SA IDs. Long-term t r e a t m e n t with allopurinol a n d / o r probenecid.

Discussion

Gout is a disorder of p u r i n e metabolism with a resulting increase in s e r u m uric acid level a n d deposits in several tissues; 10% to 2 0 % of cases may develop nephrolithiasis. In late stages, urate deposits in the kidney may lead to chronic pyelonephritis, arteriolar sclerosis, hypertension, a n d renal failure.

Atlas Links

¡ T J c f l I I PM-BC-094

GOUT

[_! X J _ IM2-052A, IM2-052B