Maester’s Collection: Cushing Syndrome

  • Central obesity, arterial hypertension, proximal muscle weakness, diabetes, oligomenorrhea, hirsutism, thin skin, and ecchymosis
  • Today, obesity is common. Anti-androgenic effects of Cushing syndrome can help differentiate it from obesity
    • +LR thin skin 112
    • +LR osteopenia 18
    • +LR ecchymoses 4
    • All 3 have a specificity of 95%
  • Prevalence of Cushing in obese/metabolic type patients 0.2%
    • 24,000 cases of Cushing/12 million patients with metabolic syndrome = 0.2%
  • 24 hour urinary free cortisol
    • 2-forms: 1) unbound to protein or 2) cortisol unconjugated to sulfuric or hyaluronic acid
    • Unbound cortisol is filtered and reabsorbed. 3% remains in urine.
    • Should measure 24-hour urine creatinine with cortisol to ensure adequate collection
      • Repeat if creatinine is less than 1.5g/day for men and 1g/day in women
    • 24-hour urine cortisol > 62mg/day has +LR 11
  • Dexamethasone Suppression test is used to differentiate ACTH dependent from ACTH independent Cushing syndrome.
    • This is now done by directly measuring ACTH levels
    • Should not be used to diagnose or screen for Cushing syndrome
      • Obese patients with depression will fail to suppress cortisol in response to dexamethasone challenge
  • For Cushingoid exam, but low or zero urinary free cortisol and suppressed ACTH levels suggests exogenous steroid and should prompt a review of medications.
  • ACTH-dependent Cushing syndrome can be due to pituitary secretion from an adenoma or ectopic secretion from a malignant source – typically in the chest.
  • Some experts recommend always doing petrosal sinus sampling due to the high prevalence of non-functioning pituitary adenomas and mortality associated with surgery. Some series report the prevalence of asymptomatic pituitary adenomas as high as 15-40%. Mortality associated with transsphenoidal micro-adenectomy is 1%.
  • ACTH-independent Cushing syndrome is usually caused by an adrenal neoplasm.
    • Characteristics of benign tumors: small (<5cm), <10 Hounsfield units, and have > 60% contrast washout at 15 minutes.
      • Benign tumors can be treated laparoscopically, while malignant tumors typically are resected with an open technique.
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Flea Bytes: Duration of NG Tubes

  • You should consider a PEG in patients who are likely to require > 4-6 weeks of feeding and there is some evidence that you should consider it at 14 days
  • Polyurethane NG tubes (Dobhoff) should be replaced every 2 weeks due to the effects of gastric acid.
  • Long term NG/NJ tubes can be kept in place for 4-6 weeks

Flea Bytes: Treating Aspiration Pneumonia

For most patients: Ampicillin/Sulbactam is sufficient for oral aerobe/anaerobic coverage

For penicillin allergic patients: Clindamycin monotherapy covers oral aerobes/anaerobes

For hospital-acquired aspiration PNA: Coverage of aerobic bacteria, especially GPC and GNR are more important than anaerobes: Pip/Tazo or meropenem monotherapy

In patients with high risk factors for MRSA, can add an agent with MRSA activity but if MRSA is not detected, this agent should be discontinued

Flea Bytes: Heavy Metal Poisoning

How do patients with heavy metal toxicity present?

Here is a quick table:

Lead: Abdominal pain, irritability, fatigue, anemia, (confusion, seizure, encephalopathy at very high levels)

Cadmium: Interstitial Nephritis

Arsenic:
Acute: Nausea, vomiting, severe watery diarrhea.

Chronic: Distal polyneuropathy

Mercury:

Acute: Chest pain, cough, dyspnea

Chronic: Mild neuropsychiatric symptoms with predominant tremor

Flea Bytes: Polymixin/Meropenem Synergy

Meta-analysis found in vitro synergy.  Especially in A baumanii. Mechanism unclear

Synergy testing can be done on isolate if available

Can not necessarily infer in vivo synergy (Beta-lactam/aminoglycoside synergy is demonstrated in vitro but NOT in vivo for example).

Systematic Review and Meta-Analysis of In Vitro Synergy of Polymyxins and Carbapenems. Antimicrobial Agents and Chemotherapy. October 2013 Volume 57 Number 10. p.5104 – 5111.

Tidings from the Citadel: Warfarin in Dialysis

Warfarin Use and the Risk for Stroke and Bleeding in Patients With Atrial Fibrillation Undergoing Dialysis – Mitesh Shah et al. Circulation. 2014;129:1196-1203.

A retrospective cohort study

Population based cohort of patients > 65 years who were admitted in Canada – Quebec and Ontario with a primary or secondary diagnosis of atrial fibrillation. Used ICD-9/10 codes to determine diagnosis and complications such as bleeding and stroke complications. Drug prescriptions were identified by database in Canada where patients > 65 have prescription benefit. Warfarin use was identified by a filled prescription within 30-days of AF diagnosis

Patients
626 dialysis patients and 204,210 nondialysis patients. Did not separate by stages of CKD, but rather HD or non-HD. Dialysis patients were younger, male, CHF, HTN, DM, CAD, and bleeding history.

Dialysis vs Non-Dialysis: CHADS2 >/= 2: 72% versus 55% (indication for anti-coagulation); HAS-BLED >/=3: 85% versus 25%. Similar rates of warfarin prescription (46% vs 51%)

image (3)

Stroke
In non-dialysis patients, warfarin users had a lower incidence of stroke (2.19 vs 2.51/100 person-years)

In dialysis patients, stroke incidence was similar for warfarin and non-warfarin users: 3.37 versus 2.91/100 person-years.

After adjusting for confounders – warfarin use had a HR of 1.14 in diaylsis patients. While in non-dialysis patients had a HR 0.87 with warfarin use.

Bleeding
After adjusting for confounders, warfarin use, was associated with a 44% higher risk for bleeding event in dialysis patients and 19% higher risk in nondialysis patients.

 

image (4)

Flea Bytes: Calf DVTs

Randomized double blind placebo-control trial that faced slow recruitment thus faces the problem of being underpowered to detect a difference.

Outpatients without cancer or prior VTE with symptomatic calf DVT. Assigned 1:1 to receive nadroparin or placebo daily for 6 weeks. All were given compression stockings and followed for 90 days.

Primary outcome was extension to proximal vein, contralateral proximal DVT, or systemic embolism by day 42.

Safety outcome – non-major bleeding by day 42.
122 patients in nadroparin and 130 placebo.

Primary outcome 3% in the nadroparin and 5% in placebo. 5 patients had bleeding in nadroparin arm with 1 major bleeding event.

Need more information before change in practice.

Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomised, double-blind, placebo-controlled trial – M Righini et al; Lancet Haematology, The, 2016-12-01, Volume 3, Issue 12, Pages e556-e562.