(BQ) Part 1 book Differential diagnosis mnemonics has contents: Introduction, pulmonary and critical care, hematology and oncology, infectious disease, cardiology, endocrinology.
- Differential Diagnosis � Mnemonics I J Differential Diagnosis Mnemonics Thomas J Donnelly, MD Pulmonary and Critical Care Consultants Dayton, Ohio Christopher C Giza, MD Assistant Researcher Division of Neurosurgery University of California Los Angeles, California HANLEY & BELFUS, INC / Philadelphia Publisher HANLEY & BELFUS, INC Medical Publishers South 3th Street Ph i ladelphia , PA 07 ( 5) 546-7293; 800-962- 892 FAX (2 ) 790-9 3 Web site: http : //www han leya ndbelfus.com Note to the reader: Although the i nformation in this book has been carefully re viewed for correctness of dosage and ind ications, neither the authors nor the ed itors nor the publ isher can accept any legal responsibil ity for any errors or om issions that may be made Neither the publ isher nor the ed itors make any warranty, expressed or i m pl ied , with respect to the material conta i ned here i n Before prescribing a n y drug, the reader m ust review the manufacturer's current product i nformation (package i nserts) for accepted ind ications, absolute dosage recom mendations, and other i nformation perti nent to the safe and effective use of the product described library of Congress Cotolog ing-in-Publ icotion Dota Donnelly, T homos J, 1962Differential Diognosis Mnemonics / Thomas J Donnelly, Christopher C Gizo p ; cm Includes bibliographical references and index ISBN 1-56053-31 1·0 lalk paper) Diagnosis, Differential Mnemonics I Giza, Christopher c., 1965II Title [DNlM: Diagnosis, Differential-Term inology-English Association Learning-Terminology-English WB 15 D685d 2000J RC71.5.D66 2001 616 07'5'014-dc21 99-088120 Differential Diagnosis Mnemonics ISBN 1-5605 3-3 1 -0 © 200 by Hanley & Belfus, Inc All rights reserved No part of this book may be reproduced , reused, republished , or transmitted in any form, or stored in a data base or retrieval system , without written permission of the publ isher Last digit is the print n umber: CO NTENTS : 2 II Pulmonary and Critical Care 1 I Introduction How to Use This Book General Approach to Differential Diagnosis Thi n king About Differential Diagnoses Presenting and Discussing Cases General Considerations General Approach to Pulmonary Med icine General Approach to Critical Care Med icine Chest X-Ray Interpretation Clinical Symptoms and Sig ns Chronic Cough Clubbing Dyspnea Hemoptysis Stridor Wheezing Clinica l Conditions or Diagnoses ARDS - Diffuse Pulmonary Infiltrates Acute Respi ratory Failure Bronchiectasis Cavitary and Cystic Lung Disease Interstitial Lung Disease Mediastinal Mass Pleural Effusion Pneumothorax ' Pulmonary Hypertension Pulmonary I nfiltrate Pulmonary Nod ule , Refractory Hypotension Sarcoidosis III HematolOgy and Oncology Genera.l Considerations Clinical Symptoms and Signs Anemia 1 13 14 16 18 19 21 23 24 27 29 30 31 33 36 38 42 ; 43 46 ! 48 50 52 55 56 Contents v i Bleed ing Diatheses Splenomegaly Clinical Conditions or Diagnoses Eosinophilia E ryth rocytosis Hypercoagula ble States Lymphopenia Monocytosis Neutropenia Neutrophilia Pa ncytopenia Throm botic Thrombocytopenic Throm bocytopenia Thrombocytosis Tra nsfusion Reactions 60 61 63 65 66 68 70 71 73 75 76 77 80 81 Purpura IV Infectious Disease Clin ical Symptoms and Signs Fever of Un known Origin Infections Causing Splenomegaly Temperature/Pulse Dissociation Clinical Conditions or Diagnoses Acute Men ing itis AI DS/ Human I m m unodeficiency Virus Immu nodeficiency States Rheumatic Fever Sexually Tra nsmitted Diseases V Cardiology Clinical Symptoms and Signs Syncope Clinical Conditions or Diagnoses Arrhyth mia Atrial Fi bril lation Congestive Heart Failure Hypotension Pericarditis Restrictive Cardiac Disease VI Endocrinology General Considerations Pituitary/Hypotha lamus Cli nical Symptoms and Signs Amenorrhea Gynecomastia Hirsutism vi • Contents 83 83 85 86 87 89 91 92 93 97 97 100 10 1 02 04 05 07 09 109 11 113 114 Cli nica l Conditions or Diagnoses Adrenal I nsufficiency Carcinoid Tumors ' Hypercalcemia Hyperphosphatemia Hyperprolacti nemia Hyperthyroidism Hypoca lcemia Hypoglycemia Hypophosphatemia Syndrome of I nappropriate Antidiuretic VI I Nephrology General Considerations Cli nical Symptoms and Signs Edema Hematuria Hypertension Clinical Conditions or Diag noses Hyperka lemia Hypernatremia Hypoka lemia Hyponatremia Neph rotic Syndrome Renal Fa ilure Renal Stones Hormone secretion 131 33 34 136 VI I I Acid-Base General Considerations Arterial Blood Gas Interpretation Clinical Conditions and Diagnoses Meta bolic Acidosis with a High Anioll Gap Meta bolic Acidosis with a Normal Anion Gap Low Anion Gap Meta bolic Alkalosis Respi ratory Acidosis Respiratory Alkalosis 38 40 43 46 49 50 152 55 55 IX Gastroenterology Clinical Symptoms and Signs Abdom inal Pa in Dia rrhea Dysphagia Hepatomega ly Jaundice Nausea and Vom iting 16 17 19 20 21 22 24 25 27 129 60 63 165 166 167 68 69 Contents ]69 73 76 178 179 18 • vii Clinical Conditions or Diagnoses Pancreatitis 83 X Rheumatology Clinical Symptoms and Signs Acute Monoarthritis Inflammatory Polyarth ritis Clinical Conditions or Diagnoses Calcium Pyrophosphate Di hydrate Deposition Disease CREST Syndrome Osteoa rthritis Rheumatoid Arthritis System ic Sclerosis (Scleroderma) Systemic Lupus E rythematosus Vasculitis Wegener's Granulomatosis XI Neurology , XII Appendix Acronym Dictionary viii • Contents 87 87 88 191 92 93 95 97 98 99 20 203 General Considerations How To Make a Broad Differential Diagnosis How To Make a "Working" Differential Diagnosis How To Do a Good Neurologic Exam ination Neurologic Exam ination Summa ry Clinical Symptoms and Signs Altered Mental Status Ataxia Autonomic Disorders Di plopia Dizziness Headache Loss of Consciousness Monocular Visual Loss Ptosis Rig idity Tremor Weakness Cl inical Conditions or Diagnoses Dementia Myelopathy Neuropathy Seizure Stroke Neurology Glossary 203 204 207 213 215 218 222 223 226 229 233 237 239 24 243 246 249 25 253 259 262 267 271 - PREFACE Generating a useful and complete differential diag nosis is a keystone of clinical medicine Many texts exist which provide exhaustive lists of possible diagnoses for a particu lar com plaint It is refining such lists into useful d ifferentials that is part of the "art" of med icine Memorizi ng lists of diagnoses can be a daunting task, and a d ry one at that By using mnemon ics as a framework, we wish to make learning differential d iagnoses more palatable and even enjoya ble In ad dition, we present an organizational a pproach to differential d iag nosis that is practical and easily learned The mnemon ics presented here range from concise lists that may be committed to memory aher the first read, to more lengthy, com prehensive listings that can be looked up when needed In al most all cases, the mnemonics themselves spell out something that refers to the symptom or diagno sis, increasing the l i kelihood of remembering it Throughout a student's medical education, he or she receives countless little tips or "pearls" that a re of im mense practical worth but are ohen difficult to look up in the Iypical medical textbook After each m nemon ic, we have i ncluded many pearls that refer to the symptom or condition descri bed Some of these tips are j ust one-l i ners; others are small tables or outl i nes that help organ ize com monly referenced i nformation We hope you find this to be a useful handbook that provides a sound organ i zational framework for a pproa c h i n g d i fferential d ia g noses The m nemonic format necessa rily led to some creative listi ngs, which should be easily remem bered as well as amusing We welcome any suggestions or new m nemonics from our readers Tom Don nelly Chris Giza Preface ix - Clinical Conditions o r D iagnoses AD R E NAL I N S U F F I C I E N CY LACKS A D R ENAL* L ow s od i u m Acidosis C a l c i u m e l eva t i o n K + e l evat i o n S ki n hype r p i g m e n t a t i o n A I t e r e d m e nta l sta t u s D e p re s s i o n R ef ractory hypote n s i o n E os i n o p h i l i a N a u s ea/a b d o m i n a l pa i n/a n o rexia A st h e n i a L o s s o f we i g h t * characteristics of adrenal insufficiency N otes Pri mary ad renocortical deficiency is rare, but secondary (due to steroid ther apy) is relatively com mon Adrenal insufficiency may be unmasked by stress due to, for example, systemic illness or infection Causes of adrenal insufficiency include anatomic destruction of the adren als (autoi m m une destructio n , surgical remova l , i nfectio n , hemorrhage, o r metastatic invasio n ) , metabolic fa i l u re (congen ita l adrenal hyperplasia o r enzyme i n h i bitors such as meta pyrone o r ketoconazole), ACTH-blocking anti bod ies, suppression of the hypothalam ic-pitu itary axis due to steroid therapy, and hypopituita rism secondary to hypothalam ic-pituitary d isease Pri mary adrenal insufficiency may be pa rt of a polyglandular autoi m m une syndrome Associated conditions i nclude lym phocytic thyroiditis, premature ovar ian fa i l u re, diabetes, and hyperthyroidism Add itional d isorders include perni cious anemia, vitiligo, alopecia, sprue, and myasthenia gravis 1 • Endocrinology Laboratory diagnosis of adrenal insuffici ency requi res ACTH sti m u lation testing to assess adrenal reserve capacity for steroid production Serum and uri nary steroid levels may be in the normal range in mild adrenal insufficiency, and therefore are not reliable for diagnosis Basal levels of cortisol and aldosterone may be subnorm a l , but defi n itive d iag nosis is obta i ned when they fa i l to i n crease after ACTH sti mu lation Consider adrenal insufficiency in any patient on steroid thera py, si nce dura tion of therapy can not rel iably predict which patients wi ll have suppression of the adrenal axis Patients on steroid therapy who have significant intercu rrent il l ness should be given stress-dose sterOids empi rica lly while acutely ill Solumed rol and pred n isone i n terfere with the ACTH sti m u lation test Hydrocortisone therapy makes i nterpretation of the test difficult, as wel l In a pa tient with suspected adrenal insufficiency, dexamethasone may be given acutely, as it will not interfere with the ACTH sti mulation test Both solumedrol and pred n isone are ulti mately converted to pred n isolone, which d i rectly i nterferes with the cortisol assay Hydrocortisone also di rectly interferes with the cortisol assay Dexa methasone does not interfere, but if it is g iven over several days it can sup press the adrenal axis Dexa methasone a lso has very l ittle mi neralocorticoid effect and may not improve hypotension as d matica lly as hydrocortisone I n critica l ly ill patients, interpretation of the ACTH sti mulation test is difficult, and free cortisol levels vary g reatly At this time, there is no convi ncing evidence that steroid supplementation is benefi cial in these patients in the a bsence of clearly demonstrable adrenal insufficiency CARCI N O I D TU M O RS 5-H IAAS H ea rt I n test i n e A i r way A st h m a S ki n N otes Carcinoid tumors a re thought to arise from neu roendocrine cel ls They syn thesize a variety of hormones a nd biogenic a m ines; the mast prominent of these Endocrinology 1 - substances is serotoni n Serotonin is meta bol ized in the body to 5-hydroxyin doleacetic acid (5-H IAAl, which is then excreted in the urine Serotonin is the ma jor med iator responsi ble for ca rd i n a l manifestations of the carcinoid syn d rome, and these five manifestations are conveniently outlined by the mnemonic "5-H IAAS " Carcinoid tumors can be found i n a number of locations The lungs, bronchi, and trachea a re the most common sites for a carci noid Other sites i nclude the stomach , d uodenum, jej u n u m , ileum, a ppendix, cecu m , colon, and rectum I n genera l , the carcinoid synd rome, with all its systemic manifestations, is seen i n patients with metastatic disease to the liver This i s thought to occur because the enteropathic circu lation normally meta bol izes the prod ucts of the carci noid tumor, thus preventing systemic symptoms Once hepatic metastases are present, the products produced by the ca rci noid tumor are released freely i nto the circu lation, avoiding hepatic clearance Carcinoid heart disease occurs in two-th i rds of patients who have the car cinoid syndrome Tricuspid reg u rg i tation and tricuspid stenosis a re the most common manifestations, but also pul monary stenosis may occur Left-sided heart disease occurs i nfrequently - i n less than 0% of patients The preponderance of lesions on the right side of the heart suggests that the heart disease is related to factors secreted into the hepatic vei n by liver metastases This concept is sup ported by the fact that the anorectic d rugs fenfl u ramine and dexfenfl u m i ne a ppear to interfere with normal serotonin metabolism and have been associated with similar cardiac va lvular lesions A second man ifestation of the carcinoid syndrome is hypotension Intesti nal manifestations include gastrOintestinal bleed i n g , obstruction , or, with the carci noid syndrome, patients may develop d iarrhea The most common type of dia rrhea is mixed secretory and hypermoti lity-induced, prod ucing watery stools un responsive to fasting Airway obstruction from a carcinoid tumor with local ized wheezing is one of the more common presentations of this tumor These a i rway tumors are very vascular and may present with hemoptysis in addition to local ized wheezi ng Asthma, with sign ificant wheezing, is another manifestation of high levels of serotonin release In addition to the a bove-mentioned loca lized wheezing from an a i rway lesion, d iffuse wheezing may occur due to bronchial hyperreactivity sti mu lated by the biogenic amines produced by the carcinoid tumor Skin manifestations are part of the classic man ifestations of the carcinoid tumor Patients have intense cutaneous flushing lasting up to several hours This involves most prom inently the face and u pper portions of the body A rare skin man ifestation of a carci noid tumor i nvolving the pancreas or g a l l bladder is necrolytic erythema Effective treatment of carcinoid tumors depends on their lo cation and symptoms Loca lized disease and rway may respond to surgical resectio n Metastatic d isease, however, prima rily involves treatment of severe symptoms associated with the carcinoid syndrome Octreotide is a potent in h ibitor of hormone secretion by carci noid cel ls, and this agent can provide ef fective control of d i a rrhea , flus h i n g , and wheezing i n as m a ny as 75% of cases 1 • Endocrinology HYPE RCALC E M IA H y p e rCALC E M IAS H y p e r pa rathyro i d i s m C a ncer A c ute re n a l fa i l u re L it h i u m C o n g e n i t a l (fa m i l i a l hypoca l c i u r i c hype rca l c e m i a ) E n d o c r i n e d i se a s e s (Ad d i s o n 's , p h eoch ro m ocyto m a , thyrotoxi c o s i s ) M i l k a l ka l a i syn d ro m e I m m ob i l iz a t i o n (exa cerbates a n o t h e r u n d e rlyi n g d i s o r d e r) A a n d D hypervita m i n o s i s S a rc o i d a n d oth e r g n u l o m a t o u s d i s e a s e s A/50 thiazide diuretics N otes Signs and symptoms of hyperca lcemia include neuromuscu lar weakness, ab' dominal pa i n , psych iatric d isturbance, renal stones , and fractures ( " bones, g roa ns, stones, and psychic moans") When hyperca lcemia is confi rmed ( usua l ly by ionized ca lcium measu re ment) , then a defin ite diagnosis must be established Primary hyperparathyroidism is the most common cause of asymptomatic hy percalcem ia in an adult Therapy for this entity depends upon the age of the pa tient and the presence of compl ications Patients under 50 years old routinely undergo surgery Other ind ications include: a Elevation of serum ca lcium more than 25-0 40 mmol/L over the upper limit of norma l b H istory of a life-threatening episode such as dehydration c DecreaSing renal function d Renal stones e Elevation of urliJ ary ca lcium > 400 mg/24 hours f Sign ificant reduction of bone mass by noni nvasive measurements Ma lig nancy-associated hypercalcemia may be due to severa l mecha nisms: a Bony invasion (e g , prostate, breast) Endocrinologv 1 - b Secretion of PTH-related prote i n ( i e , squa mous cel l a n d u roepithel ial cancers) c Production of osteoclast activating factor, which is probably interleu kin- l (i e , myeloma) Thiazide d i u retics i ncrease calci u m reu pta ke, whereas loop d i u retics (fu rosemide), after proper rehydration, promote ca lcium excretion Immobil ization does not cause hyperca lcemia alone, but may make an occult cause manifest, such as Paget's disease, hyperparathyroidism, or malignancy H Y P E R P H O S P H AT E M I A H I G H P04 PARAS H ypopa rathyro i d i s m I ntest i n a l a b so r p t i o n (vita m i n D ) G rave s' d i s e a s e H e molysis P a re n te l P04 O n co l og i c/o r g a n i n fa rction P a p rote i n A d d i so n's R e n a l fa i l u re A cidosis S a rc o i d o s i s/g n u l o m at o u s d i s e a s e N otes Hyperphosphatemia has many causes, which are outl i ned by the mnemonic "HIGH P04 PARAS " Characterized by a high level of phosphorus ( H IGH P04), one of the primary causes is hypoparathyroidism 2" Since parathyroid hormone is phosphaturic, hyperphosphatemia is a card inal feature of hypoparathyroidism A second i m portant mediator in phosphorus homeostasis is vitamin D Vitam i"n D enha nces intestinal absorption of phospho rus, and hyperphosphatemia may be seen with over-medication of vitamin D or in granulomatous diseases, in which there is enhanced conversion of vitamin D to its 120 • Endocrinology active form Si nce steroids enha nce the excretion of phosphorus into the urine, pa rticula rly mi neralocorticoids, Addison's d isease with its deficiency of steroids can result in hyperphosphatemia Graves' disease and other causes of hyperthy roidism also act to decrease renal excretion of phosphorus Enhanced cellular re lease of phosphorus may occur with tumor lysis syndrome, organ infarction, or hemolysis Hyperthyroidism also may act to increase cellular release of phospho rus An acute meta bolic or respiratory acidosis causes a cellular shift of phospho rus out of cells, lead ing to hyperphosphatemia Parenteral administration of intravenous phosphate salts or phospholi pid i nfusions can increase serum phos phorus levels Abnormal, positively cha rged serum proteins, which may occur with multiple myeloma, may cause a ma rked elevation of phosphorus These pro teins seem to have a very high-bi nding affinity for phosphorus Finally, renal fail ure is perhaps the most com mon and importa nt cause of hyperphosphatemia This is commonly managed with intesti nal phosphate-binding resins and dietary restrictions Phosphorus can be removed by dialysis only to a lim ited extent H Y P E R P R O LAC T I N E M I A PRO LACTI N S P re g n a n cy R e n a l fa i l u re O l c o nt ce pt ives a n d oth e r m e d i c at i o n s L i ver fa i l u re A d e n o m a ( p ro l a ct i n-s e c ret i n g tu m o r) C h est wa l l d i se a s e ( i n c l u d i n g h e rp e s zoste r, s u rg e ry) T hy ro i d a l d i se a s e ( hypothyro i d i s m ) I n f i ltrative d i s e a s e o f t h e p itu ita ry ( s a r c o i d o s i s , h i st i ocyt o s is N u rs i n g/n i p p l e s t i m u l a t i o n S t a l k effect X) N otes Normally, prolactin secretion by the pitu itary is restra i ned by hypotha lamic dopa m ine secretion Thus, a ny process that d isrupts hypothalamic secretion of dopamine or blocks its activity can cause hyperprolactinem ia Endocrinology 121 - Hyperprolacti nemia causes hypogonadism in men and, rarely, gynecomas tia and ga lactorrhea It commonly causes hypogonadism , a menorrhea , and galactorrhea in women; h i rsutism is rare Obtain a careful drug history Drugs that block dopamine synthesis, release, and action include phenoth iazines, butyrophenones, metoclopra mide, methyl dopa , and reserpine Estrogen sti mulation overcomes normal dopaminerg ic in hi bition This effect is only seen in hig h-dose estrogen prepa rations Estrogen a lso blocks prolactin action at the breast, preventing lactation In add ition to serum prolactin levels, la boratory evaluation includes thyroid function tests and, in the appropriate setting , renal and liver function tests Most patients requi re cranial imag ing (MRI) Any process that affects the pitu ita ry sta lk ("stalk effect") blocks dopamine se cretion , releasing the pituita ry from dopa m i nerg ic inhibition and resulting i n hy perprolacti nem ia H Y P E RTHYRO I D I S M T H E TS H T S H excess H a m b u rg e r thyrotox i c o s i s (occ u l t h o rm o n e i n ta ke) E ct o p i c thyro i d t i s s u e T hy r o i d g l a n d hyperf u n ct i o n S t i m u l a t o r of t h e thyro i d g l a n d H a s h i m oto's ( r e l e a s e o f p refo r m ed h o r m o n e ) N otes "THE TSH " refers to the first test to order when eva luating thyroid function There a re six major mechanisms of hyperthyroidism ( ) TSH excess, ( ) "ha m burger" thyrotoxicosis/occu lt sou rce of hormone, ( ) ectopic functioning thyroid tissue, (4) thyroid gland hyperfunction, (5) unregulated sti m ulators of the thyroid g land, and (6) Hashi moto's/release of preformed hormone Of these mechanisms, the latter th ree, "TS H , " a re the most com mon TSH is elevated in the first case and suppressed in the other five In addition to TSH, assays for T3 and T4 func tion , auto-a nti body titers, and possibly scintillation scann ing a re often indicated 122 • Endocrinologv In acutely ill, hospitalized patients, TSH levels may not reflect thyroid function ac cu rately and cannot be relied on TSH excess is quite rare and is caused by TSH-secreting tumors and scenarios in which the pituitary is resistant to feedback i n h i bition Hamburger thyrotoxi cosis ( ingestion of ani mal thyroid tissue) and surreptitious use of thyroid hormone (thyrotoxicosis factitia) a re secondary to an exogenous sou rce of thyroid hor mone Ectopic thyroid tissue is a rare condition in which ovarian tissue (struma ova rii) or a metastatic follicular thyroid carcinoma produces excess thyroid hor mone Thyroid gland hyperfunction occurs with a hyperfunctioning adenoma and in toxic multinodular goiter Stimulators of the thyroid gland act l i ke TSH , and the most common is the long-acting thyroid sti mu lator ( lATS) of Grave's d is ease Trophoblastic tu mors may a lso produce a n a bnormal thyroid sti m ulator Hashimoto's thyroiditis as well as irrad iation, subacute, and chronic thyroiditis cause hyperthyroidism by excessive leakage of preformed thyroid hormone into the circulation Thyroid suppressive therapy is useless in these patients, and treat ment is med at amel iorating the symptoms of thyrotoxicosis Manifestations of hyperthyroidism include nervousness, emotional labil ity, in abi lity to sleep, tremors, frequent bowel movements, sweati ng , weight loss, and heat i ntolerance Proximal muscle weakness, tremor, hyperreflexia, tachycard ia, hypertension with widened pulse pressure, and other signs of sympathetic over sti m u lation a re cha racteristic Grave's d isease patients may a lso demonstrate d isti nctive infiltrative ophthalmopathy and dermopathy In a few (usually older) patients, a clin ical picture of apathy, weight loss, and hypermeta bolism possi bly com pl icated by heart fa ilure and atrial a rrhyth mias ("a pathetic thyrotoxicosis" ) may be present A rare syndrome of hypokalemic periodic paralysis may occur in thyrotoxic patients, especially Asian and Latin American men The following m nemonic l ists most of the causes of hyperthyroidism I G ET A T S H I rrad i a t i o n G rave s' d i se a s e E xo g e n o u s h y p e rthyro i d i s m ( i od i n e , i a t rog e n i c , fact i t i o u s ) T ox i c m u lt i n od u l a r g o ite r A denoma T S H - p rod u c i n g t u m o r S u ba cute thyro i d i t i s H a s h i m oto's Also: "TSH" (Trophoblastic disease, Struma ovarii, Heparin -all very rare) Endocrinology 123 H YP O CALC E M I A IS PTH OK? I atrog e n i c S epsis P a rathyro i d ectomy/P s e u d o hy p o pa rathyro i d i s m T u m o r lys i s/T u m a H ypopa rathyro i d i s m/H ypo m a g n e s e m i a o stf; o m a l a c i a ( r i ckets) K i d n ey d i s e a s e N otes Hypocalcemia may be a tra n sient phenomena or a c h ronic conditi on C ritical to determ i n ing the cause of a low measured serum calc i u m is under standing the functional state of parathyroid hormone ( PTH; "IS PTH OK2 ") PTH acts to increase serum calcium, and in hypocalcemic states may be present, but transiently dysregulated ; a bsent; present and ineffective; or overwhelmed When interpreting the serum ca lcium, remember that a low serum a lbumin results in a low measurement of serum calc i u m An ionized ca lcium measure ment will be norma l Iatrogenic causes include tra nsfusions o f citrated blood products, plasma exchange therapy, and medications such as heparin, prota m i ne, and g lucagon These effects a re usually tra nsient and may not require treatment Sepsis and critical ill ness often a re accompan ied by a low serum calciu m , but often have normal ion ized calcium levels Pa ncreatitis ca uses a persistent low calciu m level during the acute stage for unclear reasons Treatment is prob a bly not ind icated in most patients, si nce the signs and symptoms of hypocal cemia a re a bsent Remember that IV calcium a n d hyperca lce m ic states may precipitate pancreatitis Parathyroidectomy, either intentionally or as a result of thyroid surgery, re sults in the a bsence of PTH The im mediate postoperative period presents pa rtic ular p roblems if severe bone d isease is p resent Osteitis fi bros is results from long-stand ing hyperparathyroidism, and bone m i nera l deficits a re large, result ing in the inability to respond to low serum calcium levels Pseudohypoparathyroidism is a hereditary d isease cha racterized by end organ un responsiveness to PTH PTH is present ( i n increased a mounts) and inef fective Parathyroid g land hypertrophy is present 124 • Endocrinology Tumor lysis syndrome and trauma causing rhabdomyolysis a re acute causes of hyperphosphatemia, and calci um levels fall precipitously Concomitant renal fa i l u re exacerbates the hyperphosphatemia , and PTH is overwhel med Treatment is di rected toward loweri ng phosphorous and im proving renal function Hypoparathyroidism occur as on isolated congenital defect or in asso ciation with other anomalies Acq u i red hypoparathyroidism may occur after surgery (d iscussed above) or as on autoimmune phenomenon PTH is absent or in insufficient amou nts Hypomagnesemia, when severe, is associated with hypoca lcemia due to i m paired PTH release PTH is a bsent or inappropriately low Osteomalacia (rickets) occurs when vita m i n D is absent (dieta ry, lock of sunl ight, i ntesti nal malabsorption!, defectively metabolized (a nticonvu lsa nt ther a py, vita m i n D-dependent rickets type I) or i neffective ( l iver disease, renal d is ease, vitamin D-dependent rickets type I I ) Without vitamin D, PTH is ineffective 1 Kidney disease results in phosphate retention, which lowers calci u m and interferes with conversion of 25-0H vita m i n D to its active , 25 OH form In a sense, it overwhel ms PTH and ma kes it ineffective Reduci ng dietary phosphate a n d using phosphate binders a n d calcitriol thera py a re the cornerstones of treatment H Y P O G LY C E M I A I NS U L I N O MAS I ns u l i noma N eo p l a s m ( e g , l a rg e retro p e rito n e a l t u m o rs ) S u lfony l u re a s U re m i a/re n a l fa i l u re L ive r fa i l u re I n s u l i n a nt i body syn d ro m e N ut r i t i o n ( " rea ctive hypog l yce m i a " ) O th e r d ru g s ( e t h a n o l , p r o p n o l o l , a s p i r i n ) M u n ch a u s e n 's s y n d r o m e ( s e lf-a d m i n i stered i n s u l i n ) A d re n a l i n s uff i c i e n c y ( i n c l u d i n g pa n hypo p i tu i t a r i s m ) S ta rva t i o n Also: rare hereditary enzymatic defects lL Endocrinologv 125 N otes I nsulin and sulfonylurea therapy cause the great ma jority of hypoglycemic episodes A careful assessment of medications is essentia l, as mistakes i n med ications may cause hypoglycem ia (e.g , acetyl hexa mide su bstitution for aceta zola mide) Other medications can cause symptomatic hypoglycemia such as intravenous pentamadine in AIDS patients Some drugs may have activity similar to sulfonyl u rea l agents (e.g , Bactri m l , causing hypog lycemia i n elderly or mal nourished patients Symptoms of hypoglycemia are related to epinephrine secretion and CNS g lucose deprivation A pid drop in g lucose level leads to symptoms associ ated with excess epinephrine secretion such as tachycardia, sweati ng, tremor, anxiety, and hu nger With more g radual drops, CNS symptoms predom inate, such as dizziness, headache, clouding of vision, confusion, and seizures Insulinoma is a rare tumor Levels of i nsul i n , proi nsul in and C-peptide should be obta ined duri ng hypog lycemia Demonstration of low-g lucose and h i g h-in sul i n levels during the hypoglycemic episode is not sufficient evidence for the di ag nosis of i n s u l i noma Factitious hypog lycemia from insulin i n jection or sulfonylurea d rugs is probably the most com mon cause of hypog lycemia in non diabetics Insulin injection causes a rise in insulin levels, but low C-peptide and proinsu l i n levels Most patients with insul inomas have elevated proinsu lin frac tions (> 25% of the total serum insulin) Chronic insulin in jection a lso may induce the development of anti-i nsulin antibodies Pseudohy poglycemia is a term g iven to patients who have symptoms to hours after meals, but don't have an associated low gl ucose level These pa tients may be referred for evaluation because of a spuriously low measurement It should be remembered that a pproximately 25% of normal ind ividuals have a low serum g l ucose level to hours after a meal, so this alone is insufficient to diag nose true hypoglycemia True hypog lycemia should cause symptoms and elicit a hypothalamic-pituitary response of increasing serum cortisol I n the insulin antibody syndrome, insulin is bound by the antibodies after a mea l Several hours later, the i nsulin is released and a hypoglycemic episode occurs Reactive hypoglycemia may be difficult to diag nose, and oral gl ucose toler ance testi ng is not helpfu l A high percentage of normal people demonstrate a decrease in serum glucose, si nce insulin levels normally rise after a meal Tu mors a re a rare ca use of hypog lyce m i a , and i nsuli noma is the most com mon Non-islet cell tumors ca use hypoglycemia by several mecha nisms: ( ) release of insuli n-like growth factor I I ( IGF-I I ) or its high molecu lar weight precur sor ( " b ig " IGFI, ( ) massive tumor burden with high g lucose utilization , ( ) he patic infi ltration by tumor, and (4) production of autoa nti bod ies to insulin or its receptor 126 • Endocrinology - H Y P O P H O S P H AT E M I A PHOSPHORS P a rathyro i d e ctomy H yp e rve n t i l a t i o n O n cog e n i c S ta rva t i o n -refe e d i n g P h o s p hate b i n d e rs H y p e rt h e r m i a O st e o m a l a c i a R ecove ry f r o m d i a beti c ketoa c i d o s i s S te ro i d s P H O S FAT E P a rathyro i d ectomy H ype rpa rathyro i d i s m O n cog e n i c S te ro i d s F ee d i n g A l ka l o s i s T h e r m a l i nj u ry/hype rt h e r m i a E nt e r i c ( P04 b i n d e rs , d i et a ry d ef i c i e n cy) Hypophosphatemia can be moderate or severe Severe hypophosphatemia is defined as phosphorus levels in the seru m below mM/L The effects of phosphorus depletion include rha bdomyolysis, cardiomyopathy, respiratory fail ure, eryth rocyte dysfu nction, leu kocyte dysfu nction , skeleta l deminera l ization and bone disease, nervous system dysfunction , and metabolic acidosis Hyperparathyroidism is associated with phosphorus depletion; however, after parathyroidectomy for long-standing hyperparathyroidism, " h ungry bone syn drome" may occur, and large a mounts of phosphorus may go pidly into the bone, producing clinical hypophosphatemia Hyperventilation results in a res piratory alkalosis The elevation in pH increases the rate of g lycolysis and sub sequent phosphorylation of glucose This results in an i m med iate cellular uptake of phosphorus and hypophosphatemia So-called oncogenic osteomalacia is a Endocrinology D 127 renal phosphate wasting syndrome ossociated with certa i n mesenchymal tumors It is thoug ht that an as yet u nidentified mediator promotes excessive u ri nary phosphorus loss Starvation with subsequent re-feeding also may result i n significant hypophosphatemia in the initial days o f calorie repletion T h e same effect can be seen with hyperali mentation I n chronic alcohol ics, phosphorus content is reduced i n skeletal muscles, probably because of renal phosphate losses When chron ic alcoholics go i nto withdrawal from alcohol, phosphorus may be pidly taken up into the skeleton, muscle, or liver, resulting in severe hypophosphatemia, wh ich may i n turn pre cipitate acute rha bdomyolysis Phosphate-binding a ntacids may decrease in testi nal absorption of phosphorus and lead to hypophosphatemia if overused In cases of hyperthermia, particularly the neuroleptic mal ignant syndrome, phosphate levels may fall acutely A similar phenomenon can be seen in the re covery from exhausted exercise or with severe thermal burns Osteomalacia or renal ·rickets results in renal tubular losses of phosphorus This results from a defi ciency of vita m i n D, which norma l ly promotes phosphorus absorption I n pa tients with d i a betic ketoacidosis, metabolic acidosis a n d i ns u l i n-deficiency mobil ize intracellular phosphate stores and lead to their excretion in the urine These patients a lso may have had poor nutritional i nta ke, leading to a lower level of phosphate stores When insu l i n is then administered a n d there is in creased g lucose entry in the cells, phosphorus also enters the cells, and serum hypophosphatemia may result Finally, steroid therapy, particularly aldosterone, but also glucocorticoids, tends to promote phosphate excretion into the urine and may lead to a depletion of total body phosphorus Treatment of hypophosphatemia depends on the clin ical scenario In acute symptomatic hypophosphatemia , phosphorus salts may be g iven by i ntravenous iniection In cases with coexistent hypokalemia, potassium salt may be adminis tered In treating alcoholics -who often are phosphate-, potassi um-, and mag nesium-deficient- potassium salt and magnesium su lfate may be coad ministered along with glucose 128 • Endocrinology SY N D R O M E O F I N A P P R O P R I AT E A N T I D I U R ET I C H O R M O N E S E C R ET I O N SIADH S m a l l ce l l c a rc i n o m a a n d o t h e r ca n c e rs ( p a n c re a t i c , H od g k i n 's d i s e a s e , thyro i d , d u o d e n a l ) I nfe ct i o n s ( t u b e rc u l o s i s , p n e u m o n i a , l u n g a b s c e s s ) A R D S/m echa n i c a l ve n t i l a t i o n/p u l m o n a ry d i s e a s e D ru g s H ea d t u m a/n e u ro l o g i c d i s e a s e N otes SIADH is the term applied to excessive vasopressin release associated with hyponatremia without edema U r i ne is i na ppropriately concentrated (usua l ly > 300 m mol/L) despite a low plasma osmolal ity a n d seru m sod i u m con centration Sod i u m excretion in the urine is mai nta i ned ( usua lly > 20 m mol/L) by hypervolem ia, suppression of the reni n-ang iotensin-aldosterone system, and increased levels of atrial naturietic peptide BUN and creati n i ne may decrease due to di lution SIADH may be secondary to malignancies, pulmonary diseases, d rugs, and central nervous system disorders Mal ig nancies causing S IADH include small cell carcinoma, pancreatic carcinoma, Hodg ki n's disease, thyroid carci noma , and duodenal carcinoma Pulmonary diseases causing S IADH include tubercu losis, pneu monia, and lung a bscess, as wel l as chron ic obstructive pul monary disease, ARDS, and mecha nical ventilation Drugs that may cause SIADH i n clude hypoglycem i c agents, psychotropics, na rcotics, and chemothera peutic agents Central nervous system disorders ca using S IADH incl ude head trauma, hemorrhage, encephalitis, men ingitis, Guillain-Barre, and porphyria Other causes o f euvolemic hyponatremia i nclude psychogenic polyd i psia, hy pothyroidism, adrenal insufficiency, pa in, surgery, and anesthesia SIADH should be suspected when patients have hyponatremia and a con centrated u rine (> 300 m mol /kg) in the a bsence of dehyd ratio n I m portant Endocrinology 129 - conditions to rule out include dilutional hyponatremia (such as occurs in adreno corticosteroid insufficiency), edematous states (CHF, hypothyroid ism) , hyperten sive states (renal a rtery stenosis), diuretic use, "pseudohyponatremia" (excessive plasma trig lycerides or proteins), and primary polyd i psia (a lways associated with a dilute urine, osmolal ity < 50 m mol/kg ) A water load test a s well a s urinary or plasma AVP levels a re useful i n the eva l uation In the water load test, a patient drinks a la rge volume of fluid and then urine is col lected in hou rly sa mples Normal ly, at least 65% of the water should be excreted by hours, or 80% by hours, and the lowest urine osmo lal ity (usually reached in the second hour) should be less than 00 mmol/kg Plasma AVP is i m m easura ble i n hyponatremic states, but i n SIADH it is de tecta ble even after a water load Treatment of SIADH involves relieving the underlying cause a nd fluid restriction The drug demeclocycline inhibits ADH and may be a useful treatment Some pa tients with chronic SIADH can be treated with a high sa lt and protein diet The high osmolarity will increase free water excretion 130 • Endocrinologv ... Christopher c., 19 65II Title [DNlM: Diagnosis, Differential- Term inology-English Association Learning-Terminology-English WB 15 D685d 2000J RC 71. 5.D66 20 01 616 07'5' 014 -dc 21 99-08 812 0 Differential Diagnosis. .. 83 83 85 86 87 89 91 92 93 97 97 10 0 10 1 02 04 05 07 09 10 9 11 11 3 11 4 Cli nica l Conditions or Diagnoses Adrenal I nsufficiency ... Vom iting 16 17 19 20 21 22 24 25 27 12 9 60 63 16 5 16 6 16 7 68 69 Contents ]69 73 76 17 8 17 9 18 • vii Clinical