Oligomenorrhea in the clinic!

Dr. Lesleann Hayward presented a fascinating case from clinic. A woman in her 40s presented with oligomenorrhea x4 years without weight loss, excessive exercise, galactorrhea, hirsutism, or menopausal sx. BMI, TSH, prolactin were normal. FSH was inappropriately normal with a very elevated estrogen level (like 2000s). Transvaginal US surprisingly didn't show any endometrial thickening but noted numerous ovarian cysts. Testosterone level was normal suggesting against PCOS. The patient's estrogen level continued to rise but normalized after stopping her biotin supplement and starting on low-dose OCPs. Though this case still leaves us puzzled, it was a great refresher on how to work up amenorrhea and oligomenorrhea in the clinic. When in doubt, no one will fault you for involving gynecology or endocrinology.

Let's refresh with some definitions:

Amenorrhea: lack of menses.

  • primary: lack of menses by age 15 or age 13 is no breast development (usually an anatomic, genetic, or hormone deficiency an d not discussed here as not typically seen in adult world). If uterus is absent, get a karyotype to evaluate for Turners.
  • secondary: absence of menses for >3 months in women who previously had a regular menstrual cycles OR absence of menses for > 6 months in woman with previously irregular menstrual cycles.

Oligomenorrhea: fewer than nine menstrual cycles per year or cycle length greater than 35 day


In thinking of possible pathology, it can be helpful to think of the hypopituitary axis and what can go wrong at each level.

 
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However a more practical approach is to get standard amenorrhea labs and work through this algorithm for cause. (fun exercise to test your understanding of the hypothalamic-pituitary-ovarian axis!)

Let's order some labs:

The initial labs for someone with amenorrhea or oligomenorrhea is a beta-HCG (VERY important), prolactin, TSH, FSH, LH, estrogen (+ testosterone if hirsutism). Remember, low BMI, excessive exercise, and eating disorders can also cause amenorrhea so get a thorough history.

Read our next blog   on the pains of biotin supplementation on hormone lab assays which was felt to be a confounder in this case.    A progesterone challenge can be considered to see if someone is progesterone deficient (will bleed within 5 days of giving progesterone). This suggests eugonadotrophic amenorrhea and should raise concern for structural abnormalities and suggests the patient is making estrogen but is anovulatory.    Resources:   UpToDate:  Welt and Barbieri. “ Evaluation and management of secondary amenorrhea.” UpToDate. 5/2018.    AAFP:  Klein, et al. “Amenorrhea: A Systematic Approach to Diagnosis and Management.” AAFP. 7/2019.  https://www.aafp.org/afp/2019/0701/p39.html

Read our next blog on the pains of biotin supplementation on hormone lab assays which was felt to be a confounder in this case.

A progesterone challenge can be considered to see if someone is progesterone deficient (will bleed within 5 days of giving progesterone). This suggests eugonadotrophic amenorrhea and should raise concern for structural abnormalities and suggests the patient is making estrogen but is anovulatory.

Resources:

UpToDate: Welt and Barbieri. “Evaluation and management of secondary amenorrhea.” UpToDate. 5/2018.

AAFP: Klein, et al. “Amenorrhea: A Systematic Approach to Diagnosis and Management.” AAFP. 7/2019. https://www.aafp.org/afp/2019/0701/p39.html

African Tick Bite Fever

Dr. Westwood presented a great case of a patient who had just returned from traveling on Safari to Sub-Saharan Africa who presented with acute fevers, chills, drenching night sweats and an exquisitely painful erythematous/violacious left first metatarsal rash. He was initially admitted to the vascular surgery service and underwent CTA of the lower extremity and TTE without evidence of thrombus and was started on cefazolin and a heparin drip. Over the course of the next coming days, his cellulitis quickly spread more proximally and he was started on vancomycin and piperacillin tazobactam. Unfortunately, despite broad spectrum antibiotics, the erythema continued to spread and inflammatory markers continued to rise. General surgery had also evaluated the patient and did not feel like he warranted a surgical intervention?

What’s your summary statement and what’s your differential for a worsening cellulitis despite broad spectrum antibiotics?

We don’t see these types of things very often. Here’s a resource to help us form our differential

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ID and dermatology was consulted. ID recommended starting the patient on doxycycline for atypical coverage. A skin biopsy revealed: neutrophilic dermatitis with vascultitis + papillary edema with ? ecthyma, negative for bacterial/fungal/AFB. After addition of doxycycline, his rash started to regress. 2 weeks later, a broad range PCR returned positive for Rickettsia Africae

Liver Abscess

Dr. Johnny Cai presented a case of a woman with a history of a pancreatic tail cyst who had two weeks of progressive RUQ pain, fever, and night sweats. She was hemodynamically stable, but her labs revealed a hepatocellular liver injury and a severe leukocytosis. RUQ ultrasound revealed pneumobilia without common bile duct dilatation, cholelithiasis or pericholecystic fluid.

Pneumobilia, you say?

The differential for pneumobilia is short -- post-procedural vs BADNESS (like gas-producing bacterial infection).

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The team then proceeded with a CT (shown here):

“gas and fluid filled structure 5x4 cm in segment 4 of the liver consistent with abscess without clear source.”

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When thinking about a liver abscess, it can be helpful to try to classify it further into pyogenic (most common) vs less common causes such as amebic or unusual infections (TB, Echinococcus, candidal). Your history should alert you if you should be thinking about atypical liver abscesses. Echinococcus has a very distinct look on imaging and should not be aspirated for culture as this can be lethal.

You should also ensure you get blood cultures as liver abscesses can form from hematogenous spread.

A liver abscess?

The patient was started on pipercillin/tazobactam and IR aspirated the liver abscess and placed a drain. The aspirate culture never grew anything (suspected sterilized with antibiotics).

Her leukocytosis was not improving and thus she was -reimaged without change in abscess and had another drain placed. THIS IS A GOOD TEACHING POINT: if the clinical picture isn’t improving, make sure you truly have source control (drain not in right place, another process going on, wrong antibiotics, etc.) After her clinical picture started to improve, she was transitioned to metronidazole and moxifloxacin to complete a 6 week course.

References:

  • UptoDate “Pyogenic Liver Abscess”

  • Lübbert C, Wiegand J, Karlas T. Therapy of Liver Abscesses. Viszeralmedizin. 2014;30(5):334–341

  • Rathimian, J et al. Clinical Infectious Diseases. 2004 Dec 1;39(11):1654-9

  • Tan YM, Chung AY, Chow PK, et al. Ann Surg. 2005;241(3):485–490

  • Wong, Wai Man et al. Journal of Gastroenterology and Hepatology. (2002) 17, 1001–1007

Fatigue and Hemochromatosis

Dr. Chandrashekar presented a case of a man with heavy alcohol use who presented to primary care clinic for fatigue. Work-up was revealing for hepatocellular liver injury and an elevated transferrin saturation leading to a workup for hereditary hemochromatosis.

Transferrin saturation= Iron/TIBC x 100

As a reminder, there are many causes of elevated ferritin (including liver disease) which was highlighted on another blog post from June. Ferritin is an acute phase reactant and it is not enough to diagnosis someone with hemochromatosis.

To diagnosis someone with iron overload you need a transferrin saturation of >45% (AASLD). Many labs do not calculate a transferrin sat so you may miss this if you aren't thinking about hemochromatosis when your iron studies return. Transferrin sat can be falsely elevated in settings where there is acute increase in iron (such as hemolysis or oral iron intake).

The work up for fatigue starts with a good history. In patient's with fatigue, hemochromatosis should be considered particularly if a patient has liver disease or diabetes without traditional risk factors. As highlighted in this case, many patient's liver disease is attributed to their alcohol use when in reality hemochromatosis is also at play.

The illness script for hemochromatosis:

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40-50 yo Caucasian man (or post-menopausal female) with fatigue, chronic liver disease, diabetes, arthritis, and hyperpigmentation. Other organs include endocrine glands (pituitary, pancreas, thyroid, hypothyroid, etc) and infiltrative cardiomyopathy.

More on Hereditary Hemochromatosis:

  • the HFE gene is the most common cause of hereditary hemochromatosis. The HFE gene is autosomal recessive. However, the gene has low penetrance, so even patients with homozygosity may not have phenotypic disease.
  • alcohol use is common in patient hemochromatosis with evidence of liver disease in part because of the "two hit" hypothesis. This concept is common in hepatology in which a liver is vulnerable due to an underlying disease (such as hemachromatosis) and another injury (such as alcohol) causing inflammation and injury can lead to clinicial disease.
 

One more small but important hint in this case:

PAPPENHEIMER BODIES!

on the peripheral smear.

What are pappenheimer bodies you may be asking?They are iron inclusion bodies in RBCs (look like Heinz bodies but stain positive for iron). If you see this on a peripheral smear you should question if the patient has splenic dysfunction or if there is an issue with hemolysis or excess iron.

Pappenheimer bodies can be seen in:

  • asplenia
  • spenic dysfunction such as MDS
  • sickle cell disease
  • sideroblastic anemia
  • lead poisoning
  • hemochromatosis

Hyperkalemia Master Class

Dr. Levin presented a case of a patient who had “changes on tele” and ended up having this EKG:

Yikes! He had a normal EKG prior.   Let’s point out some of the scary changes here:   1. Where are the P waves? are they gone entirely or just very small?  2. Are those T waves peaked?  3. Why is the QRS suddenly so wide?

Yikes! He had a normal EKG prior.

Let’s point out some of the scary changes here:

1. Where are the P waves? are they gone entirely or just very small?

2. Are those T waves peaked?

3. Why is the QRS suddenly so wide?

Labs were obtained and he had a K of 7.6!

Here’s our approach to the evaluation of hyperkalemia:

(Content adapted from the excellent curbsider’s podcast: Hyperkalemia Master Class)

  1. Does it make sense for this patient to have hyperkalemia?

    • Is the sample hemolyzed?

    • If not, consider causes of pseudohyperkalemia: ie very high WBC count like in CLL, thrombocytosis (PLT >1,000,000), anything that increases the likelihood of the cells lysing in the phlebotomy tube

  2. Rule out urinary obstruction (if anyone can comment on the mechanism of this, please do in the comments section! For a prize of resident education …okay and some candy too)

  3. Evaluate for hyperglycemia (can ca

When do we treat?

  • In one study by Einhorn et al:

    • Potassium 5.5 OR for death

    • Potassium >6, OR for death 31

  • Consider treating (ie shifting etc) when K>6.0 + EKG changes or >6.5 regardless of EKG changes

What do we treat ACUTELY with?

  • Calcium for membrane stabilization (Calcium gluconate typically but Calcium chloride is also an option)

  • Insulin & glucose (Don’t forget to recheck glucose q30-60min after for up to 3-4 hours!)

  • Beta agonist (The dose of albuterol for shifting is 20mg. To give you an idea, the dose of a standard albuterol neb is 2.5mg)

  • Bicarb (typically reserved for when the cause of the hyperkalemia is acidosis. Keep in mind also that bicarb will shift calcium into cells— something you may not want in the setting of EKG changes)

But how do we get it out of the body?

  • If they can pee, urine is the best bet (lasix or lasix + IVF so minimize the adverse side effects of the diuretics)

  • Reserve kayexylate (or SPS) for those who cannot urinate or those who have chronic hyperkalemia. AVOID this in patients w/ CKD or ESRD, s/p renal transplantation or any kind of bowel obstruction/decreased bowel motility (refer to our recent blog post here

Thanks for reading! If you’re enthralled and need to know MORE about hyperkalemia, we highly recommend the hyperkalemia master class episode of the Curbisider’s Podcast here

Pneumatosis Intestinalis

Dr. Haraga presented a case of a man with vascular disease and end-stage renal disease (ESRD) who recieved sodium-polysytrene-sulfonate for hyperkalemia. One day later he developed fever, hypotension and acute on chronic RLQ pain without diarrhea or hematochezia. CT showed pneumatosis coli. The differential included colonic necrosis from sodium-polystyrene sulfonate vs ischemic colitis given his comorbidities. At this point, the etiology remains unclear, but the patient improved with antibiotics for sepsis of unclear (but suspected abdominal) source.

Pneumatosis Intestinalis: It literally means gas in the wall of the small or large intestine. The differential for pneumatosis intestinalis is vast. To quote the an article from the American Journal of Roentgenology, etiologies range from "benign to life-threatening." History and risk factors are the key to discerning cause and need for acute workup.

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Pneumatosis Intestinalis can be seen on abdominal x-ray or CT and is characterized by “thumbprinting.” On exams, it is classically associated with pseudomembranous colitis. Here are some actual photos of thumb-printing (the example from noon report was incorrect).

A note about sodium-polystyrene-sulfonate:

Intestinal necrosis is a rare side effect of SPS, but the risk is not zero. Many studies associate the SPS + sorbitol formulation as having the highest risk, and the FDA has removed sorbitol from SPS formulations. However, it is unclear if sorbitol alone was the clear culprit. At this point it is wise to avoid SPS in patients with altered gut motility (see below).

There is one small case series of patients with ESRD showing no development of colonic necrosis with daily low-dose sorbitol-free SPS. However, this is not standard of care, and hemodialysis is still the best way to normalize potassium in patients with ESRD.

As a general rule, AVOID sodium-polystyrene-sulfonate (SPS) in:

  • post-operative patients

  • patients with ileus or receiving chronic opioids

  • patients with large or small bowel obstruction

  • patients with underlying bowel disease (UC, crohn’s, C diff)

  • patients with ESRD where iHD is readily available.

"Spells"- a clue in elderly patients

Dr. Manley presented a case of an elderly man with history of dementia and visual hallucinations (small children running around) who was admitted for “spells”. These spells were short lived, characterized by sudden staring off, occasional atonia, occasional urinary incontinence, some extremity jerking and absence of post-ictal state.

…. Does this illness script jog anyone’s memory?

What if I told you that this was his orthostatic vitals:

  • Lying: 107/64, HR 82

  • Standing 1 min: 97/50, HR 84

  • Standing 3 min: 79/42, HR 86

…Anything strike you about the heart rate?

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Now what's on your differential for neurodegenerative disease + autonomic failure?

  • PARKINSON’S DISEASE: motor symptoms predominate, 20-60% patients will develop autonomic failure

  • LEWY BODY DEMENTIA: next slide

  • MULTIPLE SYSTEMS ATROPHY: dysautonomia, motor symptoms, oculomotor issues, and urinary incontinence- challenging to differentiate from Parkinson’s. Preserved cognitive function + minimal response to Levodopa are clues

  • PURE AUTONOMIC FAILURE: isolated dysautonomia without other symptoms, good prognosis

This patient had likely LEWY BODY DEMENTIA! We characterized these “spells” as “cognitive fluctuations”.

“like” this post if you got the diagnosis right!

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Agranulocytosis and a word on Bronchiectasis

Dr. Kiefer presented a thought provoking case of a patient with chronic saccular bronchiectasis who presented with agranulocytosis and fevers! Let’s review:

What’s agranulocytosis? I remember learning that in med school…

It’s when neutrophilia gets bad:

  • Mild: Absolute neutrophil count (ANC) <1500

  • Moderate: ANC 500-1000

  • Severe: ANC <500 *

  • Agranulocytosis: ANC<200 **

* ANC <500 + fever (T>38.2 OR >38 degrees for greater than an hour) is neutropenic fever

** Agranulocytosis is caused by medications up to 70% of the time (most commonly: sulfasalazine, TMP-SMX, methimazole (these three are responsible for up to 42% of cases). Other ones on the list include NSAIDs, macrolides, vancomycin (Commonly USED ones just to keep in mind).

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Figure 1: Algorithm for the evaluation and treatment of adult patients with neutropenia ( Gibson, C., & Berliner, N. (2014). How we evaluate and treat neutropenia in adults. Blood, 124(8), 1251-1258. Accessed August 11, 2019.https://doi.org/10.1182/blood-2014-02-482612.)

Ok, now how do I think about etiologies of bronchiectasis?

Very briefly, we can categorize conditions associated with bronchiectasis into the following categories: Post-infectious, congenital conditions, immunodeficiencies, sequelae of toxic inhalation/aspiration, rheumatologic conditions.

Please refer to this review article by our very own Alan Barker, MD for details!

Barker, A. (2002). Bronchiectasis. N Engl J Med, 346:1383-1393

https://www.nejm.org/doi/10.1056/NEJMra012519

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