Board Review-Internal Medicine

Ranjita Pallavi, MD

Internal Medicine

PGY 3

• A 67-year-old woman is evaluated for a 2-day history of severe muscle weakness. The patient experienced significant weight gain and developed hypertension and type 2 diabetes mellitus 2 years ago. She also reports developing muscle weakness of the lower extremities 6 month ago. Her diabetes is only partially controlled by metformin; her blood glucose measurements at home are usually greater than 250 mg/dL (13.9 mmol/L). Other medications are hydrochlorothiazide, lisinopril, amlodipine, and metoprolol.

• Physical examination shows a woman who appears chronically ill. Blood pressure is 154/92 mm Hg, and other vital signs are normal; BMI is 40. Skin examination is notable for facial hirsutism. Central obesity, mild proximal muscle weakness, and 2+ peripheral edema are noted.

• Results of laboratory studies show a serum creatinine level of 1.3 mg/dL (115 µmol/L), a plasma glucose level of 144 mg/dL (8.0 mmol/L), and a serum potassium level of 2.9 meq/L (2.9 mmol/L).

• Which of the following tests should be performed to reveal the cause of her diabetes?

1. Adrenal CT

2. C-peptide measurement

3. Glutamic acid decarboxylase antibody titer

4. Pancreatic MRI

5. 24-Hour urine free cortisol excretion

• Signs and symptoms with high discriminatory index for Cushing’s syndrome:

• Proximal muscle weakness• Thin skin• Plethora• Easy bruising• Thick red or purple striae• Osteoporosis

• A 44-year-old man is evaluated for a 2-year history of headache and 1-year history of diabetes mellitus and hypertension. His glove and shoe sizes have increased several times over the past 3 years, and he reports painful knees and hips. The patient also has sleep apnea and carpal tunnel syndrome. Medications are metformin and lisinopril.

• On physical examination, blood pressure is 152/92 mm Hg, pulse rate is 82/min, and respiration rate is 16/min. Coarse facial features, frontal bossing, accentuated nasolabial folds, a large tongue, and thick hands and feet are noted.

• Which of the following is the most appropriate next diagnostic test?

1. MRI of the pituitary gland

2. Random serum growth hormone measurement

3. Serum insulin-like growth factor 1 measurement

4. Serum prolactin measurement

• 48 year old woman presents to diabetes clinic for uncontrolled diabetes. She has DM for 3 years, treated with Glyburide and metformin. HbA1C 7.7%. Complaints include frequent ER visits for panic attacks with palpitations, headaches, diaphoresis and labile hypertension. Plasma and urine metanephrines are elevated.

• What is the most likely diagnosis?

• 44 year old man referred for new onset diabetes. Treated for bipolar disorder with quetiapine for 6 years. Developed weight gain, hypertension and dyslipidemia controlled with niacin, simvastatin, atenolol and HCTZ. Recently developed a rash and started on cyclosporin. 6 months prior: FBG 113 mg/dl, HbA1C 6.1, today FBG 181 mg/dl and A1C 7.9.

• What is the most likely diagnosis?

Drug-Induced Hyperglycemia: who is at risk?

1. 1st degree relatives with diabetes

2. High risk race/ethnicity (African, Indian, Asian, Pacific Islander)

3. PCOS

4. Prior gestational diabetes

5. Hypertension, low HDL (<35 mg/dl) or high TG (>250 mg/dl)

6. A1C >5.7, IGT or IFG

7. Insulin resistance (acanthosis nigricans, obesity, sedentary)

Drug-Induced Hyperglycemia

1. Pentamidine

2. Glucocorticoids

3. Calcineurin inhibitors

4. Atypical antipsychotics

5. Protease inhibitors

6. Thiazides

7. Beta blockers

8. Niacin

9. Phenytoin

Thiazide-Induced Hyperglycemia

1. Dose dependent effect

2. Minimal risk at doses commonly used to treat HTN

3. Degree of hyperglycemia correlates with that of hypokalemia

4. 45% increase in RR for new-onset diabetes for every 0.5 mEq/L decline in serum K

5. K supplementation may decrease

6. risk of incident diabetes

Glucocorticoid-Induced Hyperglycemia

• Mechanism involves mainly insulin resistance, but at high doses also decreased insulin secretion

• Risk of diabetes determined by dose, duration, and baseline risk of patient

• GC worsen hyperglycemia in virtually all diabetics• In non-diabetics odds ratio of developing new-onset diabetes after

GC is 1.5 – 2.5• FPG may not be sensitive for diagnosis • Screening with post-prandial glucose is recommended• Diet and exercise often not effective or practical treatment options

• A 46-year-old man is hospitalized for a subarachnoid hemorrhage after collapsing shortly after developing a severe headache. He has stage 2 chronic kidney disease due to autosomal dominant polycystic kidney disease. He also has hypertension managed with enalapril.

• Mechanical ventilation is initiated, and a ventriculostomy drain is placed. Sedation is maintained with propofol and morphine, and he is treated with fosphenytoin for seizure prophylaxis.

• On physical examination, temperature is 35.8 °C (96.4 °F), blood pressure is 126/70 mm Hg, and pulse rate is 96/min. Cardiac and pulmonary examinations are normal.

• Patient’s plasma is noted to be lipemic in appearance.• Which of the following is the most likely cause of this patient's

laboratory findings?

1. Fosphenytoin

2. Propofol

3. Propylene glycol

4. Pyroglutamate

• Increased serum osmolal gap with or without high-anion-gap metabolic acidosis can be an important clue to toxic alcohol intoxications

• The presence and magnitude of serum osmolal gap depends on several factors, including molecular weight of the offending alcohol, baseline serum osmolal gap, and state of metabolism of the parent alcohol

• Patients with toxic alcohol intoxications can present with an increase in serum osmolality alone, increased serum osmolality and high-anion-gap acidosis, or increased-anion-gap acidosis alone. Rare cases in which both serum osmolality and anion gap are within reference ranges also might occur

• Kidney failure, lactic acidosis, and diabetic ketoacidosis also can cause high-anion-gap metabolic acidosis associated with a large serum osmolal gap

• Given the potential severity of all these disorders, they should be excluded in all individuals presenting with serum osmolal gap and high-anion-gap metabolic acidosis, or high-anion-gap metabolic acidosis alone

• 50 year old male patient has DM for past 8 years and is on Insulin treatment. Annual microalbuminuria screening reveals an ACR of 5mg/mmol. Patient does not have any evidence of CKD. His BP is well controlled.

• What should be the next step?

• When implementing blockade of the renin–angiotensin system start treatment with an ACE inhibitor first then move to an ARB if the ACE inhibitor is not

tolerated.• Offer ACE inhibitors/ARBs to people with diabetes and ACR more than 2.5 mg/

mmol (men) or more than 3.5 mg/mmol (women) irrespective of the presence

of hypertension or CKD stage.• Offer ACE inhibitors/ARBs to non-diabetic people with CKD and hypertension

and ACR 30 mg/mmol or more (approximately equivalent to PCR 50 mg/mmol

or more, or urinary protein excretion 0.5 g/24 h or more)• Offer ACE inhibitors/ARBs to non-diabetic people with CKD and ACR 70 mg/

mmol or more (approximately equivalent to PCR 100 mg/mmol or more, or

urinary protein excretion 1 g/24 h or more) irrespective of the presence of

hypertension or cardiovascular disease.

• ACE inhibitors and ARBs can be used safely in most patients with CKD.• They should be used at moderate to high doses, as used in clinical trials.• ACE inhibitors and ARBs can be used in combination to lower blood pressure or

reduce proteinuria.• Patients treated with ACE inhibitors or ARBs should be monitored for hypotension,

decreased GFR, and hyperkalemia.• In most patients, the ACE inhibitor or ARB can be continued if:• a GFR decline over 4 months is <30% from baseline value;• b Serum potassium is ≤5.5 mEq/L.

• 78 year old Indian male is brought to the ER with complaints of headaches, poor oral intake, vomiting for 1 week associated with confusion. GCS 13. On exam he is found to have palatal asymmetry and loss of gag reflex. He is moving all 4 extremities. DTR are brisk but symmetrical. Right extensor plantar response+. PMHx HTN, DM. CSF shows 1200 WBC, total protein 110g/L, lymphocyte predominant, mildly decreased glucose levels.Brain CT shows basal meningeal enhancement.

• What should be the next step?

• Clinical stages — It is useful for prognosis and therapy to categorize patients on presentation by the stage of illness, based upon the mental status and focal neurologic signs.

1. Stage I patients are lucid with no focal neurologic signs or evidence of hydrocephalus.

2. Stage II patients exhibit lethargy, confusion; may have mild focal signs, such as cranial nerve palsy or hemiparesis.

3. Stage III represents advanced illness with delirium, stupor, coma, seizures, multiple cranial nerve palsies, and/or dense hemiplegia.

• Characteristic CSF findings of TBM include the following:(i)lymphocytic-predominant pleiocytosis. Total white cell counts are usually between 100 and 500 cells/μL. Very early in the disease, lower counts and neutrophil predominance may be present,(ii)elevated protein levels, typically between 100 and 500 mg/dL,(iii)low glucose, usually less than 45 mg/dL or CSF: plasma ratio <0.5.

• Classic neuroradiologic features of TBM are basal meningeal enhancement and hydrocephalus .

• Hypodensities due to cerebral infarcts, cerebral edema, and nodular enhancing lesions may also be seen.

• Magnetic resonance imaging (MRI) is the imaging test of choice for visualizing abnormalities associated with TBM, as it is superior to computed tomography (CT) for evaluating the brainstem and spine.

• The T2-weighted MRI imaging has been shown to be particularly good at demonstrating brainstem pathology; diffusion-weighted imaging (DWI) is best at detection of acute cerebral infarcts due to TBM. However, CT is adequate for urgent evaluation of TBM-associated hydrocephalus for possible surgical intervention.

• Suggested approach — Treatment begins with an ‘intensive phase’ which consists of a four drug regimen that includes INH, RIF, PZA, and either EMB or STM, administered daily for two months. This is followed by a ‘continuation phase’ which consists of INH and RIF alone if the isolate is fully susceptible, either administered daily or three times a week.

• Duration of therapy — Therapy should be administered for 9 to 12 months in drug-sensitive infections. If PZA is omitted or cannot be tolerated, treatment should be extended to 18 months.

• The antituberculous chemotherapy regimen for clinical tuberculoma is the same as for meningitis, except that duration of treatment is extended to 18 months

• Specific clinical indications for adjunctive steroid therapy based upon urgent warning signs include:

• Patients who are progressing from one stage to the next at or before the introduction of chemotherapy, especially if associated with any of the conditions listed below.

1. Patients with an acute "encephalitis" presentation, especially if the CSF opening pressure is ≥400 mm H2O or if there is clinical or CT evidence of cerebral edema

2. Patients who demonstrate "therapeutic paradox," an exacerbation of clinical signs (eg, fever, change in mentation) after beginning antituberculous chemotherapy

3. Spinal block or incipient block (CSF protein >500 mg/dL and rising)

4. Head CT evidence of marked basilar enhancement (portends an increased risk for infarction of the basal ganglia) or moderate or advancing hydrocephalus

5. Patients with intracerebral tuberculoma, where edema is out of proportion to the mass effect and there are any clinical neurologic signs (altered mentation or focal deficits).

• Glucocorticoid regimen — Either dexamethasone or prednisone may be used, as follows:

• Dexamethasone –Adolescents and adults >25 kg: 0.3-0.4 mg/kg/day for two weeks, then 0.2 mg/kg/day week three, then 0.2 mg/kg/day week four, then 4 mg per day and taper 1 mg off the daily dose each week; total duration approximately eight weeks.

• Prednisone –Adolescents and adults: 60 mg/day. Administer initial dose for two weeks, then taper gradually over the next six weeks (ie reduce daily dose by 10 mg each week); total duration approximately eight weeks.

• Surgery — • Patients with hydrocephalus may require surgical decompression of

the ventricular system.• In patients with clinical stage II disease, the combination of serial

lumbar puncture and steroid therapy may suffice while judging the early response to chemotherapy.

• However, surgical intervention should not be delayed in patients with stupor and coma or when the clinical course on therapy is marked by progressive neurologic impairment .

• 50 year old female patient is admitted to MICU for septic shock secondary to multi-lobar pneumonia. She needs venous access for close hemodynamic monitoring. What preventive measures can decrease the rate of CLABSI in her?

Preventive measures for CLABSI include:

• Choosing appropriate sites for catheter insertion• Using the appropriate type of catheter material• Using barrier precautions during insertion• Changing catheter administration sets at appropriate intervals• Ensuring proper catheter-site care• Ensuring removal of catheters when no longer essential

DETERMINANTS OF INFECTION RISK 

• 3 major determinants of infection risk with intravascular catheters:

1. Type of catheter

2. Location of catheter placement

3. Duration of catheter placement

Risk of CLABSI

• Peripherally inserted midline catheters – 0.2 (95% CI 0.0-0.5)• Peripheral intravenous catheters – 0.5 (95% CI 0.2-0.7)• Peripherally inserted central catheters – 1.1 (95% CI 0.9-1.3)• Cuffed and tunneled central venous catheters – 1.6 (95% CI

1.5-1.7)• Arterial catheters for hemodynamic monitoring – 1.7 (95% CI

1.2-2.3)• Noncuffed central venous catheters• Nonmedicated and tunneled – 1.7 (95% CI 1.2-2.3)• Nonmedicated and nontunneled – 2.7 (95% CI 2.6-2.9)• Pulmonary artery catheters – 3.7 (95% CI 2.4-5.0)

• Duration — The duration of catheterization has been considered an important risk factor for infection with both peripheral venous and arterial catheters. The risk of infection has been reported to increase after the following intervals:

• Peripheral venous catheter – greater than three to four days • Central venous catheter – greater than six days • Pulmonary artery (Swan-Ganz) catheter – greater than three to four

days • Arterial catheter – greater than four to six days