Uveitis

DEFINITION
Uveitis is an inflammation of the uveal tract, including the iris, ciliary body, and choroid. It may also involve other closed structures, such as the sclera, retina, and vitreous humor.
PHYSICAL FINDINGS AND CLINICAL PRESENTATION
● Symptoms of uveitis depend on the site of involvement and whether the process is acute or insidious.
● Acute anterior uveitis: pain and photophobia. Vision may not be affected initially.
● Posterior uveitis: fl oaters, hazy vision. Involvement of the retina may produce blind spots or fl ashing lights.
● Insidious anterior uveitis: symptoms may not be present until scarring cataracts and loss of vision occur.
● Photophobia
● Blurred visual acuity
● Irregular pupil
● Hazy cornea
● Abnormal cells  and flare in anterior chamber or vitreous humor
● Retinal hemorrhage, vascular sheathing
● Conjunctival injection
● Ciliary fl ush
● Keratitic precipitates (precipitates on the cornea; )
● Hazy vitreous
● Retinal infl ammation
● Iris nodules
● Glaucoma
● Rheumatoid arthritis
● Scleritis
● Systemic symptoms related to cause


CAUSE
● Infections: herpes simplex virus, cytomegalovirus, toxoplasmosis, tuberculosis, syphilis, HIV
● Systemic disorders: sarcoidosis, Behçet’s syndrome, HLAB27– associated diseases (e.g., ankylosing spondylitis, reactive arthritis), inflammatory bowel disease, juvenile idiopathic arthritis
● Idiopathic
● A comprehensive history is essential for determining the cause of uveitis.

DIFFERENTIAL DIAGNOSIS
● Glaucoma
● Conjunctivitis
● Retinal detachment
● Retinopathy
● Keratitis
● Scleritis
● Episcleritis
● Masquerading syndromes: lymphoma, uveal melanoma, metastases (breast, lung, renal), leukemia, retinitis pigmentosa, retinoblastoma
LABORATORY TESTS
● CBC
● Laboratory tests for specific inflammatory causes (e.g., ANA,ESR, VDRL, HLA-B27, purifi ed protein derivative [PPD], Lyme titer)
● Visual field testing; slit-lamp examination, indirect ophthalmoscopy.
IMAGING STUDIES
● Chest x-ray in suspected sarcoidosis, tuberculosis (TB), histoplasmosis
● Sacroiliac x-ray in suspected ankylosing spondylitis.

TREATMENT
● Treat the underlying disease. Treatment is often multidisciplinary (ophthalmologist, internist, rheumatologist, infectious disease [ID] specialist).
● Treat photophobia and local pain.
● Acute general medical therapy
● Corticosteroids are the mainstay of therapy for noninfectious causes.
● Antibiotics for bacterial infections and antiviral agents, when viral infection is suspected, should be started to prevent retinal damage.
● Systemic steroids, if appropriate for the underlying disease. Systemic corticosteroid therapy is generally reserved for patients with systemic disorders and those with bilateral disease refractory to local medication or those with major ocular disability or retinitis.
● Antimetabolites, when indicated. Immunosuppressive medications used in steroid-dependent or refractory uveitis include methotrexate, sulfasalazine, azathioprine, cyclosporine, and tacrolimus. These medications can have signifi cant toxicity and should be prescribed only by physicians experienced with their use.

Human immunodeficiency virus

THE ASYMPTOMATIC HIV-INFECTED PATIENT
● The human immunodeficiency virus, type 1 (HIV) causes a chronic infection that culminates, usually after several years, in acquired immunodefi ciency syndrome (AIDS).
● Acute infection occurs 2 to 6 weeks from the time of viral transmission.  illustrates the kinetics of viral
load and immune response during the phases of HIV-1 infection.
● The acute infection most often is a mild, self-limited mononucleosis-like illness; pharyngitis, mucosal ulcerations
, rash , penile ulcer from sexual contact , splenomegaly, and lymphadenopathy commonly occur. Hepatitis and aseptic meningitis are occasionally seen.
● The p24 antigen and the HIV polymerase chain reaction (PCR) will be reactive ; positive HIV serology
usually first becomes positive 1 month later.

● CD4 cells subsequently decline an average of 75/mm3 per year, but the range is variable. Five percent of infected people are long-term nonprogressors; another 10% progress more rapidly.


CAUSE
● RNA retrovirus HIV-1  was probably derived from transmission of a simian immunodeficiency virus (SIV) from chimpanzees in Central Africa; a related virus HIV-2 was derived from an SIV found in Sooty Mangebey
monkeys from West Africa.
● HIV-1 is the predominant pathogenic retrovirus in human populations; HIV-2 has limited distribution (primarily in West Africa) and tends to be less rapidly immunosuppressive than HIV-1.
● Transmitted by sexual contact, shared needles, blood transfusion, or from mother to child during pregnancy, delivery, or breastfeeding.
● Primary target of infection: CD4 lymphocyte .
● Direct central nervous system (CNS) involvement: manifested as encephalitis , myelopathy, or neuropathy
in advanced cases
● Renal failure , rheumatologic disorders, thrombocytopenia, or cardiac abnormalities

DIFFERENTIAL DIAGNOSIS
● Acute infection: mononucleosis or other respiratory viral infections
● Late symptoms: similar to those produced by other wasting illnesses such as neoplasms, tuberculosis (TB), disseminated fungal infection, malabsorption, or depression
● HIV-related encephalopathy: confused with Alzheimer’s disease or other causes of chronic dementia; myelopathy and neuropathy possibly resembling other demyelinating diseases such as multiple sclerosis,

LABORATORY TESTS
Three HIV viral antibody screening tests currently are in use:
● ELISA
● Bound anti-HIV antibody is detected by antihuman antibody labeled with an enzyme. The use of recombinant proteins has reduced false-positive results (specificity, 99.9%).
● A false-negative finding may result when measured in the acute infection period (sensitivity, 99.9%).
● New rapid serologic-screening assays
● HIV-antigen–coated gelatin or latex particle agglutination assays. The single-use test can be performed rapidly but may be less sensitive and specifi c than standard ELISA tests.
● A oral salivary test called OraSure (sensitivity, 99.9%) is sent to a reference laboratory after being inserted into the
mouth for 2 minutes.
● Western blot confirmatory test  is performed when ELISA is positive.
● This test identifies specifi c viral antigens; it is positive when both core and envelope antigens are present.
● The result is indeterminate when either antigen is present; if unchanged when repeated in 6 months in more than
one laboratory, this is considered a false-positive result.

Management Strategies for the Asymptomatic Patient
● Initial testing: CD4 cell count and HIV viral load measured every 3 to 6 months to guide decisions regarding antiretroviral use and prophylaxis against PCP and MAC infection
● Other testing: identifi es previously acquired latent infections that may become reactivated because of loss of T cell
function but can be prevented by the use of specific agents
● Serology to Toxoplasma gondii (IgG):
● Clinical infection may be prevented by trimethoprimsulfamethoxazole (TMP-SMZ) used as prophylaxis for PCP.
● Venereal Disease Research Laboratories (VDRL) test:
● Lumbar puncture should be performed in patients with a confirmatory specifi c test (FTA).
● Treatment with intramuscular benzathine penicillin if the CSF fluid is normal, and intravenous penicillin for 10
days if the CSF VDRL test is reactive or CSF pleocytosis, protein elevation, or hypoglycorrhachia is present.
● PPD skin test showing induration of 5 mm or greater, or patients with exposure to someone with active tuberculosis
● Treatment with isoniazid 300 mg/day for 9 months or, in case of isoniazid-induced hepatitis, rifampin 600 mg PO qd (only for those not receiving protease inhibitors or nucleoside reverse transcriptase inhibitor agents) for 4 months

Hyperlipidemia

DEFINITION
Hyperlipidemia can be defined as an abnormal elevation of plasma cholesterol or triglyceride levels. It is a major contributor to atherosclerosis  and coronary thrombosis. The composition of the major classes of lipoproteins
is depicted .
PHYSICAL FINDINGS AND CLINICAL PRESENTATION
● Most patients: no physical fi ndings
● Possible fi ndings particularly in the familial forms
1. Tendon xanthomas
2. Xanthelasma
3. Arcus corneae
4. Eruptive xanthomata on the buttocks
5. Lipemia retinalis
6. Milky appearance of plasma
CAUSE
Primary
● Genetics
● Obesity
● Dietary intake
Secondary
● Diabetes mellitus
● Alcohol
● Oral contraceptives
● Hypothyroidism
● Glucocorticoid use
● Most diuretics
● Nephrotic syndrome
● Hepatoma
● Extrahepatic biliary obstruction
● Primary biliary cirrhosis


DIAGNOSTIC APPROACH
● Serum total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides should be measured in all
adults 20 years of age and older at least once every 5 years, particularly if there is a history of premature coronary artery disease in a fi rst degree relative.
● LDL can be measured directly or calculated by using the following formula if the triglyceride levels are lower than 400 mg/dL:

LDL cholesterol total cholesterol  HDL cholesterol  (triglycerides/5)
● All patients should be assessed for the presence of coronary heart disease risk factors and diabetes.
MEDICAL MANAGEMENT OF LIPID DISORDERS
● Dietary treatment is the cornerstone of therapy to reduce blood lipid levels and to promote weight loss in the overweight patient.
● Drug therapy is initiated when lifestyle changes are insufficient to achieve desired lipid levels. Several medications are now available for treatment.
● Lipid-lowering agents
1. Statins (3-hydroxy-3-methyglutaryl coenzyme A [HMGCoA] reductase inhibitors) are effective and generally well
tolerated and are agents of choice in patients with elevated LDL cholesterol levels unresponsive to dietary restrictions.
They can decrease LDL cholesterol by 20% to 60%, increase HDL cholesterol by 5% to 15%, and decrease triglycerides by 10% to 40%. All statins necessitate frequent monitoring of liver function tests (alanine aminotransferase [ALT], aspartate transaminase [AST]) for potential toxicity. Concomitant use of cyclosporine, fibrates, niacin, or erythromycin can increase the risk of myopathy.

HDL cholesterol
● Lipid management guidelines recognize the importance of HDL levels by raising the threshold of low HDL cholesterol to 40 mg/dL and award a negative risk factor (removes one risk factor from the total count) for HDL cholesterol 60 mg/dL. Each increase in serum HDL level of 1 mg/dL is associated with a 2% to 4 % reduction in cardiac events.
● Aerobic exercise and modest intake of ethanol will raise HDL levels. Regular aerobic exercise increases the HDL cholesterol level by 3% to 9% in healthy sedentary persons.
Obesity and cigarette smoking are associated with reduced HDL cholesterol. Diet rich in omega-3 polyunsaturated fatty acids with limited carbohydrates will increase HDL.
● Therapy with nicotinic acid (20% to 35 % increase), fibrates (10% to 25% increase), or statins (2% to 15 % increase)
will increase HDL levels. Use of fibrates or niacin is recommended for persons whose HDL is lower than
40 mg/dL and who have diabetes mellitus or the metabolic syndrome.

Hypoglycemia and insulinoma

DEFINITION
● Hypoglycemia can be arbitrarily defined as a plasma glucose level less than 50 mg/dL. To establish the diagnosis, the following three criteria are necessary:
1. Presence of symptoms:
● Adrenergic: sweating, anxiety, tremors, tachycardia, palpitations
● Neuroglycopenic: seizures, fatigue, syncope, headache, behavioral changes, visual disturbances, hemiplegia
2. Low plasma glucose level in symptomatic patient
3. Relief of symptoms after ingestion of carbohydrates
● Insulinoma is a pancreatic insulin-secreting tumor that causes symptoms associated with hypoglycemia.

CLASSIFICATION
Reactive hypoglycemia
● Hypoglycemia usually occurs 2 to 4 hours after a meal rich in carbohydrates.
● These patients have no symptoms in the fasting state and rarely experience loss of consciousness secondary to their
hypoglycemia because the glucose level rarely goes below 40 mg/dL.
● Patients who have had subtotal gastrectomy rapidly absorb carbohydrates, causing an early and very high plasma
glucose level, followed by a late insulin surge that reaches its peak when most of the glucose has been absorbed. This results in hypoglycemia.
● Patients with type 2 (non–insulin-dependent) diabetes can experience hypoglycemia 3 to 4 hours postprandially
secondary to a delayed and prolonged second phase of insulin secretion.
● Congenital defi ciencies of enzymes necessary for carbohydrate metabolism and functional (idiopathic) hypoglycemia are additional causes of reactive hypoglycemia.
Fasting hypoglycemia
● Symptoms usually appear in the absence of food intake (at night or during early morning).
● Cause: insulinoma, mesenchymal tumors that synthesize insulin-like hormones, adrenal failure, glycogen storage
disorders, severe liver or renal disease.
Iatrogenic or drug-induced
● Hypoglycemic drugs (e.g., sulfanylureas)
● Excessive insulin replacement
● Factitious
● Ethanol-induced hypoglycemia
● In the hospital setting, a common cause of hypoglycemia is putting noncompliant patients on the regimen that they
are supposed to be on at home, not realizing that the patient has been noncompliant.
● Hypoglycemia has also been associated with the use of the antibiotics gatifloxacin and levofloxacin.


DIAGNOSIS
● In a healthy person, when the plasma glucose level is low (e.g., fasting state), the plasma insulin level is also low. The following measurements taken during the hypoglycemic episode are useful in patients presenting with unexplained hypoglycemia:
1. Plasma insulin and proinsulin levels
2. C-peptide (connecting peptide)
3. Plasma and urine sulfonylurea levels
● Factitious hypoglycemia should be considered, especially if the patient has ready access to insulin or sulfonylureas (e.g., medical or paramedical personnel, family members who are diabetic or in the medical profession).
1. To diagnose factitious hypoglycemia secondary to sulfonylureas, screen serum and urine to determine the presence of sulfonylureas.
2. To diagnose factitious hypoglycemia secondary to insulin, the following measurements may be obtained:
● Insulin level, which is markedly increased following exogenous insulin injection; the proinsulin level, however, is
decreased.
● Insulin antibodies: this test was once considered evidence of factitious hypoglycemia when animal insulin was the
only commercial form available. Patients self-administering insulin currently may have no detectable insulin antibodies because of the use of human insulin. Therefore, this test is of limited use in cases of factitious hypoglycemia.
● C-peptide: insulin is synthesized by the pancreas as a single-chain polypeptide formed of A and B chains joined
by the C-peptide. This single-chain polypeptide (proinsulin) is broken down and secreted into the bloodstream as
insulin and C-peptide in a 1:1 ratio. Exogenous insulin does not contain C-peptide; thus, C-peptide levels are elevated in patients with insulinoma and sulfonylureas but not after exogenous insulin injection.
3. Pancreatic islet cell neoplasms (insulinomas) are usually small (3 cm), single, insulin –producing adenomas. Insulinomas are almost always solitary. Malignant insulinomas account for 5% of the total; they tend to be larger
(6 cm). Metastases are usually to the liver (47%), regional lymph nodes (30%), or both. Measurement of inappropriately elevated serum insulin levels, despite an extremely low plasma glucose level after prolonged fasting (24 to 72 hours), is pathognomonic for these neoplasms.
IMAGING STUDIES
● Abdominal CT scanning or MRI  detects one half to two thirds of insulinomas (abdominal ultrasound is not effective). It should be done only after laboratory tests for insulinoma have confi rmed the diagnosis
● The insulinoma can often be located by selective pancreatic
arteriography
TREATMENT OF INSULINOMA
● Enucleation of single insulinoma
● Partial pancreatectomy for multiple adenomas
● Carbohydrate administration
● Diazoxide directly inhibits insulin release and has an extrapancreatic hyperglycemic effect that enhances glycogenolysis.
● Lanreotide and octreotide (somatostatin analogues)
● Streptozotocin.

Hypogonadism

CAUSE
Hypergonadotropic hypogonadism
● Hormone resistance (androgen, luteinizing hormone insensitivity)
● Gonadal defects (e.g., Klinefelter’s syndrome, myotonic dystrophy)
● Drug induced (e.g., spironolactone, cytotoxins)
● Alcoholism- or radiation-induced
● Mumps orchitis
● Anatomic defects, castration


Hypogonadotropic hypogonadism
● Pituitary lesions (neoplasms, granulomas, infarction, hemochromatosis, vasculitis)
● Drug-induced (e.g., glucocorticoids)
● Hyperprolactinemia
● Genetic disorders
1. Laurence-Moon-Biedl syndrome: rare autosomal recessive trait combining retinitis pigmentosa, hypogonadism, developmental delay, and spastic paraplegia
2. Prader-Willi syndrome: disorder characterized by severe hypotonia at birth, severe obesity , short stature (responsive to growth hormone), small hands, and mental retardation. In patients with Prader-Willi syndrome,
both hypogonadotropic hypogonadism and hypergonadotropic hypogonadism, perhaps secondary to cryptorchidism,
have been reported. More than 50% of children have a chromosomal deletion involving band q11.2 of the long arm of
chromosome .
3. Delayed puberty
4. Other: chronic disease, nutritional deficiency, Kallmann’s syndrome, idiopathic isolated luteinizing hormone or
follicle-stimulating hormone deficiency.
PHYSICAL FINDINGS AND CLINICAL MANIFESTATIONS
● Nonspecific symptoms associated with testosterone deficiency include depression and irritability.
● Long-standing hypogonadism of all causes can result in
characteristic fine facial wrinkling .
● The prepubertal testis measures some 2 cm in length and increases to 4.1 to 5.5 cm in the normal adult. When the
seminiferous tubules are damaged before puberty, the testes are small and firm.
● Postpubertal damage characteristically causes small, soft testes. Considerable testicular damage can occur before the overall size is below the lower limits of normal.

● Breast enlargement is a common feature of feminizing states in men and may be an early sign of androgen deficiency.
Treatment 
● Variable with cause

Turner’s syndrome Management

DEFINITION
Turner’s syndrome refers to a pattern of malformation characterized by short stature, ovarian hypofunction, loose nuchal skin, and cubitus valgus.
PHYSICAL FINDINGS AND CLINICAL PRESENTATION
● Turner’s phenotype is recognizable at any point on the developmental
spectrum .
● In spontaneous abortions, the most common sex chromosome abnormality detected (45,X chromosome constitution) is found in 75% of affected individuals and accounts for 20% of such cases.
● In fetuses, it is suspected because of ultrasonographic manifestations such as thickening of the nuchal folds, frank nuchal cystic hygromas, or mild shortness of the femora at midtrimester.
● In infants
1. At birth, may display loose nuchal skin (pterygium colli) and edema on the dorsa of the hands and feet
2. Canthal folds refl ecting midface hypoplasia and redundant skin in the periorbital region
3. Nipples appearing widely spaced
4. Heart and cardiovascular system: murmur of aortic stenosis or bicuspid aortic valve or diminished femoral pulses
suggestive of aortic coarctation.
5. Renal ultrasonography: renal ectopia, such as pelvic kidney or horseshoe kidneys
● In older children
1. Slow linear growth
2. Short stature: may be improved with growth hormone therapy
3. Delayed or absent menses: secondary sex characteristics possibly normalized with estrogen replacement therapy
4. Intelligence is often normal, but delays in spatial perception or visual motor integration are commonly observed;
frank mental retardation is rare.


CAUSE
● Phenotype caused by absence of the second sex chromosome, whether X or Y
● 45,X chromosome constitution in about 50% of affected individuals
● Other chromosome aberrations (40% of cases): isochromosome Xq (46,X,i[Xq]) or mosaicism (XX/X)
● With deletions involving the short (or p) arm of the X chromosome: short stature but little ovarian hypofunction
● Deletions involving Xq13-q27: ovarian failure
● Usually a defi ciency of paternal contribution of sex chromosome, reflecting paternal nondisjunction
DIFFERENTIAL DIAGNOSIS
● Noonan’s syndrome, an autosomally dominant inherited disorder also characterized by loose nuchal skin, midface
hypoplasia, canthal folds, and stenotic cardiac valvular defects and affecting males and females equally; also has normal chromosome constitutions
● Other conditions in the differential diagnosis of loose skin, whether or not associated with edema:
1. Fetal hydantoin syndrome (loose nuchal skin, midface hypoplasia, distal digital hypoplasia)
2. Disorders of chromosome constitution (trisomy 21, tetrasomy 12p mosaicism)
3. Congenital lymphedema (Milroy edema)
WORKUP
● Giemsa-banded karyotype to confi rm clinical diagnosis
● Once diagnosis is established: cardiologic consultation for evaluation for cardiac valvular abnormalities or aortic coarctation
● Renal ultrasonography
● Endocrine evaluations in older patients with short stature or amenorrhea
● Psychometrics to document known or suspected learning disabilities.
LABORATORY TESTS
● As noted, routine Giemsa-banded karyotype on peripheral lymphocytes to confi rm the clinical impression in all suspected cases of Turner’s syndrome
● Recognition of associated medical problems, such as hypergonadotropic hypogonadism or autoimmune thyroiditis,
prompting periodic evaluation of these potential areas.

IMAGING STUDIES
● Echocardiography
● Renal ultrasonography
● Abdominal ultrasonography for evaluation of ovarian and uterine size and morphology
● MRI of brain (especially in cases with known or suspected neurologic impairment)
● Radiography (for evaluation of carpal, metacarpal abnormalities, radioulnar synostosis)
● Bone age (for evaluation of short stature)
TREATMENT
● General medical care guided by normal medical standards, with special attention paid to identifying such agerelated problems as developmental delays, learning disabilities, slow growth, amenorrhea

Diabetes mellitus

DEFINITION
Diabetes mellitus (DM) refers to a syndrome of hyperglycemia resulting from many different causes. It can be classified into type 1 (formerly insulin-dependent diabetes mellitus [IDDM]) and type 2 (formerly non–insulin-dependent diabetes mellitus [NIDDM]). Because insulin-dependent and non–insulindependent refer to the stage at diagnosis, when a type 2 diabetic needs insulin, he or she remains classifi ed as type 2 and does not revert to type 1.
The American Diabetes Association (ADA) defi nes DM as (1) a fasting plasma glucose 126 mg/dL, (2) a nonfasting
plasma glucose 200 mg/dL, or (3) glucose 200 mg/dL in the 2-hour sample in an oral glucose tolerance test (OGTT). Furthermore, a value of 100 mg/dL of fasting blood sugar is the upper limit of normal for glucose. A fasting glucose between 100 and 126 mg/dL is classifi ed as impaired fasting glucose (IFG).

CAUSE
Idiopathic diabetes
TYPE 1 DIABETES MELLITUS
● Hereditary factors
1. Islet cell antibodies (found in 90% of patients within the first year of diagnosis)
2. Higher incidence of HLA types DR3, DR4 3. 50% concordance in identical twins
● Environmental factors: viral infection (possibly coxsackie virus, mumps virus)
TYPE 2 DIABETES MELLITUS
● Hereditary factors: 90% concordance in identical twins
● Environmental factor: obesity

Diabetes secondary to other factors
● Hormonal excess: Cushing’s syndrome, acromegaly, glucagonoma, pheochromocytoma
● Drugs: glucocorticoids, diuretics, oral contraceptives
● Insulin receptor unavailability (with or without circulating antibodies)
● Pancreatic disease: pancreatitis, pancreatectomy, hemochromatosis
● Genetic syndromes: hyperlipidemias, myotonic dystrophy, lipoatrophy
● Gestational diabetes

DIFFERENTIAL DIAGNOSIS
● Diabetes insipidus
● Stress hyperglycemia
● Diabetes secondary to hormonal excess, drugs, pancreatic disease
PHYSICAL FINDINGS AND CLINICAL PRESENTATION
● Physical examination varies with the presence of complications and may be normal in early stages.
● Diabetic retinopathy
● Nonproliferative (background diabetic retinopathy)
1. Initially: microaneurysms (Fig. 285–1), capillary dilation, waxy or hard exudates, dot and fl ame hemorrhages , arteriovenous (AV) shunts 2. Advanced stage: microinfarcts with cotton-wool exudates, macular edema
● Proliferative retinopathy: characterized by formation of new vessels , vitreal hemorrhages, fibrous scarring,
and retinal detachment
● Cataracts and glaucoma occur with increased frequency in diabetics.
● Peripheral neuropathy: patients often complain of paresthesias of extremities (feet more than hands); the symptoms are symmetrical, bilateral, and associated with intense burning pain (particularly during the night).
● Mononeuropathies involving cranial nerves III, IV, and VI, intercostal nerves, and femoral nerves are also common.

TREATMENT
● Diet
● Calories
1. The diabetic patient can be started on 15 cal/lb of ideal body weight; this can be increased to 20 cal/lb for an active
person and 25 cal/lb if the patient does heavy physical labor.
2. The calories should be distributed as 50% to 60% carbohydrates, less than 30% fat, with saturated fat limited to less than 10% of total calories, and 15% to 20% protein.
3. The emphasis should be on complex carbohydrates rather than simple and refi ned starches and on polyunsaturated instead of saturated fats in a ratio of 2:1.
● Seven food groups
1. The exchange diet of the ADA includes protein, bread, fruit, milk, and low- and intermediate-carbohydrate vegetables.
2. The name of each exchange is meant to be all-inclusive (e.g., cereal, muffins, spaghetti, potatoes, rice are in the
bread group; meats, fish, eggs, cheese, peanut butter are in the protein group).
3. The glycemic index compares the rise in blood sugar after the ingestion of simple sugars and complex carbohydrates with the rise that occurs after the absorption of glucose.
Equal amounts of starches do not produce the same increase in plasma glucose (pasta equal in calories to a baked
potato causes less of an increase than the potato). Thus, it is helpful to know the glycemic index of a particular food
product.
4. Fiber: insoluble fi ber (bran, celery) and soluble globular fiber (pectin in fruit) delay glucose absorption and attenuate the postprandial serum glucose peak. They also appear to lower the elevated triglyceride level often present in uncontrolled diabetics. A diet high in fiber should be emphasized (20 to 35 g/day of soluble and insoluble fiber).

Gynecomastia

DEFINITION
Excessive breast tissue growth in a male.
CAUSE
● Stimulatory and inhibitory hormones control the growth and differentiation of mammary tissue in the male .
● Estradiol binds to estrogen receptors and stimulates glandular cells, whereas testosterone exerts a generalized inhibitory action on growth and differentiation.
● The balance between stimulatory and inhibitory hormones controls the development and maintenance of breast tissues.

DIAGNOSIS
● The diagnosis between physiologic and pathologic gynecomastia in adult men presents a challenge because of the
common presence of breast enlargement in normal men and its association with obesity

● Important aspects of the history and physical examination in gynecomastia are described in Box 284–1.
● A method of examination for detecting gynecomastia .

● Pathologic gynecomastia  is defined as palpable breast tissue larger than 4 cm in diameter, palpable breast
tissue larger than 2 cm that is tender, or palpable tissue larger than 2 cm demonstrated to be gradually increasing in
diameter on follow-up.
● Mammography may occasionally be necessary to make this distinction, particularly in obese patients .
DIAGNOSIS
● Elimination of contributing factors
● Surgical correction


Cause 

Estradiol excess Estradiol secretion:

adrenal tumors Sporadic testicular tumors (sex cord, Sertoli cell, germ cell, Leydig cell)
Testicular tumors associated with familial syndromes (Peutz-Jeghers, Carney’s complex)
-Hepatic tumor with aromatase
-Increased aromatase activity
-Exogenous estrogens or estrogenic substances: drug therapy with estrogens
-Estrogen creams and lotions
-Occupational exposure to various estrogenic substances
-Cannabinoids
-Estrogen analogues: digitoxin
-Elevated estrogen precursors, aromatizable androgens: human chorionic gonadotropin (hCG) excess (eutopic or ectopic); exogenous hormones—testosterone enanthate, testosterone propionate, anabolic steroids, hCG administration.

Testosterone deficiency
Estradiol, testosterone imbalance Drugs: cytotoxic drug-induced hypogonadism from busulfan, vincristine, nitrosourea, vincristine; combination chemotherapy; steroid synthesis inhibitory drugs
Androgen resistance: complete testicular feminization
-Partial: Reifenstein’s, Lubb’s, Rosewater’s, and Dreyfus syndromes
-Androgen antagonists: cimetidine, spironolactone, fl utamide, bicalutamide, cyproterone acetate Blockers of               5-reductase
-Regulatory hormone excess Drug therapy with catecholamine antagonists or depleters, sulpiride, metoclopramide;
phenothiazines, reserpine, domperidone, tricyclic antidepressants, methyldopa, haloperidol
-Other causes: local trauma, hip spica cast, chest injury, herpes zoster of chest wall, post-thoracotomy, spinal cord injury
-Other chronic illnesses: renal failure, pulmonary tuberculosis, HIV, diabetes mellitus, leprosy, refeeding, gynecomastia
-Drugs associated with gynecomastia with strong relationship of effect: amiodarone, calcium
channel blockers, fi nasteride

Hirsutism

DEFINITION
Hirsutism is the development of stiff, pigmented (terminal) facial  and body hair in women as a result of excess
androgen production.
PHYSICAL FINDINGS AND CLINICAL PRESENTATION
● Timing of symptoms: abrupt onset, short duration, rapid progression, progressive worsening, more severe signs
of virilization, or later age at onset suggest androgenproducing tumor, late-onset is more common with congenital
adrenal hyperplasia, or Cushing’s syndrome. Weight increases may produce increased androgen production.
● Menstrual history: menarche, cycle regularity and symptoms of ovulation, fertility, and contraception use. Anovulatory cycles are the most common underlying cause of androgen excess.
● Medication use history: some drugs cause hirsutism or produce androgenergic effects (e.g., danazol, phenytoin, androgenic progestins [norgestrel], cyclosporine, minoxidil, metoclopramide, phenothiazines, methyldopa, diazoxide, penicillamine).
● Family history: known or suspected family history of hirsutism, congenital adrenal hyperplasia, insulin resistance,
PCOS, infertility, obesity, menstrual irregularity.
● Physical examination: voice, body habitus, galactorrhea, abdominal and pelvic examination.
● Associated cutaneous manifestations: acne, acanthosis nigricans, striae, hair distribution, location and quantity, frontotemporal balding, muscle mass, clitoromegaly.

CAUSE
● Presence of hirsutism indicates androgen excess. Total testosterone may be normal, but free testosterone is elevated.
● Anovulatory ovaries are the usual source of excess androgens through thecal cell steroidogenesis and conversion of
androstenedione to testosterone.
● Conditions that decrease hepatic production of sex hormone-binding globulin (SHBG) decrease protein-bound
testosterone and increase free testosterone fraction (e.g., low estrogen, high androgen, and hyperinsulinemic states).
● Late-onset, congenital adrenal hyperplasia enzyme deficiency (most commonly, 21-hydroxylase defi ciency) produces excess 17 hydroxyprogesterone (17-OHP) and overproduction of androstenedione. These defects affect glucocorticoid, mineralocorticoid, and sex steroid pathways. Excessive accumulations of dehydroepiandrosterone (DHEA), a weak androgen , and defective conversion to the potent androgens result in partial virilization in both females and males. Females have labial fusion, clitoral hypertrophy, and modest hirsutism, which may progress. Males have hypospadias, bifid scrotum, and a small phallus.
● Rare ovarian tumors, primarily derived from Sertoli-Leydig cells, granulosa theca cells, or hilus cells, produce excess androgens.

These rare tumors should be considered in any woman who presents with rapid onset of hirsutism or virilization
or evidence of hyperestrogenism. Fewer than 1% of ovarian tumors are endocrine-secreting. Sertoli-Leydig and Leydig cell tumors are the most common androgen-secreting tumors of the ovary. Adrenal-like tumors of the ovary are extremely rare. With all functional tumors of the ovary, surgical removal leads to a rapid improvement in symptoms .
● Rare adrenal tumors produce excess androgens.
● Rare pituitary or hypothalamic tumors produce excess prolactin and can lead to anovulation.
DIFFERENTIAL DIAGNOSIS
● Androgen-independent vellus hair: soft, unpigmented hair that covers entire body.

LABORATORY TESTS
● Total serum testosterone or free testosterone-screen for testosterone secreting tumors. If markedly elevated, may image adrenals and ovaries.
● DHEA-S (DHEA sulfate): screen for adrenal androgen production because this is almost entirely produced by adrenals.
● Prolactin: moderately elevated values should prompt imaging of pituitary-hypothalamic region.
● 17-OHP (17-hydroxyprogesterone): screen for adrenal enzyme deficiencies.

TREATMENT
● Weight reduction: can reduce androgen production, improve menstrual function, and slow hair growth in obese
women
● Cosmetic: temporary
● Shaving: does not stimulate hair growth; lasts days
● Epilation: electronic plucking
● Bleaching
● Mechanical waxing, plucking
● Depilatories: chemically disrupts sulfide bonds of hair, causing dissolution of hair shaft
● Pulsed laser: good for pigmented hair; lasts 3 to 6 months
● Cosmetic: permanent
● Electrolysis: destroys individual hair follicles
● Combined energies: bipolar radio frequency and pulsed light
● Cosmetic-eflornithine topical 13.9% cream: temporary. Hair growth returns on discontinuation of treatment; slow response over 4 to 8 weeks; applied directly to unwanted facial hair twice daily, with at least 8-hour spaced applications
● Suppress ovarian steroidogenesis and LH through low-dose estrogen and low androgenic progestational agents: slow response to treatment, suppresses new hair growth, established hair unaffected
● Spironolactone (aldosterone-antagonist diuretic inhibits adrenal and ovarian biosynthesis of androgens ): when oral contraceptive pills (OCPs) unacceptable, or may be added for disappointing results after 6 months of OCP treatment.

Placenta previa

DEFINITION
Placenta previa is the implantation of the placenta over the internal os. Four degrees of this abnormality have been defined:
● Total placenta previa: the internal os is covered completely.
● Partial placenta previa: the internal os is partially covered.
● Marginal placenta previa: the edge of the placenta is at the margin of the internal os.
● Low-lying placenta: the placenta is implanted in the lower uterine segment, and although its edge does not reach the internal os, it is in close proximity to it.
PHYSICAL FINDINGS AND CLINICAL PRESENTATION
The classic presentation of placenta previa is painless vaginal bleeding, usually in the second or third trimester. Uterine contractions may or may not be present. On physical examination, the uterus is soft and pain free. The fetus is often in breech, transverse lie, or high. Fetal distress is usually not present.
CAUSE
Uncertain


DIFFERENTIAL DIAGNOSIS
● Placenta accreta
● Placenta percreta
● Placenta increta
● Vasa previa
● Abruptio placentae
● Vaginal or cervical trauma
● Labor
● Local malignancy

WORKUP
● Do NOT perform a digital vaginal examination.
● The diagnosis of placenta previa can seldom be firmly established by physical examination alone. A speculum examination in a hospital setting to exclude any local bleeding may be performed.
● This diagnosis should not be dismissed until a thorough evaluation, including sonography, has completely excluded
its presence.
LABORATORY TESTS
● A CBC can be used to monitor hemoglobin and hematocrit.
● A Kleihauer-Betke preparation of maternal blood in all Rhnegative women and Rh-immune globulin when indicated.
IMAGING STUDIES
● The simplest, most precise, and safest method of placental localization is transabdominal sonography with confirmatory imaging by transvaginal ultrasonography. Transperineal sonography has also proved effective in detection.
● MRI has also been effective in detecting placenta previa, although sonography remains the preferred method.
TREATMENT
● In preterm pregnancies with no active bleeding, close observation and expectant management are indicated. In those with active bleeding, conservative management, including blood transfusions for severe bleeds, is appropriate. The woman should stay in the hospital for at least 48 hours after the bleeding has stopped.

● Bed rest, preferably in a hospital setting, should be prescribed.
● Initial assessment for signs of maternal hemodynamic compromise or hemorrhagic shock; large-bore intravenous access with crystalloid fluid resuscitation
● Assess fetal status and gestational age using sonogram and continuous fetal heart rate monitoring
● Cross-matched blood should be made available during bleeding episodes; if the hemorrhage is severe, cesarean delivery is indicated despite fetal immaturity
● Tocolytic therapy may be considered in those women in preterm labor, as well as the administration of corticosteroids to enhanced fetal lung maturity
● Cesarean delivery is necessary in nearly all cases of placenta previa.
● Uncontrollable hemorrhage after placental removal should be anticipated secondary to the poorly contractile nature of the lower uterine segment. The need for hysterectomy to control bleeding should be discussed with the patient before delivery, if possible.