A Weighty Issue

This week in Morning Report, we discussed the case of a young woman who presented with 3-4 months of weight gain, irregular menstruation, acne, increasing facial hair, and fatigue. We initially thought of a diagnosis of Polycystic Ovarian Syndrome, or PCOS (common things being common)…but this wouldn’t be an internal medicine case if there wasn’t more to the picture!

We further discussed some history, physical examination, and lab findings that prompted this patient’s specialist team to eventually land on an uncommon diagnosis: ACTH-Dependent Cushing’s Syndrome from an ectopic source. Read on ahead for a few key learning points from this case.

What, you mean you DIDN’T memorize the adrenal steroidogenesis pathway in med school (along with the Krebs cycle and the coagulation cascade)?! Image from Wikimedia Commons.

1. PCOS is a common, poorly understood, and heterogenous diagnosis with many mimickers

PCOS is the most common endocrinopathy to affect young women of childbearing age, and is a significant contributor to infertility. Diagnosis of PCOS is based on the Rotterdam criteria, which requires two of the following 3 criteria:

  • Androgen excess (biochemical or clinical)
  • Ovulatory dysfunction
  • Ultrasound findings of polycystic ovaries

To avoid premature diagnostic closure and to ensure we don’t miss life-threatening diagnoses, it is useful to review the Endocrine Society guideline on PCOS, which recommends excluding the following diagnoses in all women investigated for PCOS:

Diagnoses to exclude in ALL patients being investigated for PCOS, as per Endocrine Society guidelines

In addition to the above mandatory testing, you must do a carefully history and physical examination looking for other mimickers of PCOS. We went through a detailed diagnostic approach, which I’ve outlined in a flowchart below:

Clues on history/physical that guide you towards other important PCOS mimics. Adapted from Endocrine Society Guidelines on Diagnosis and Treatment of PCOS, 2013.

2. Approach to Cushing’s syndrome

In our case, our patient had a history and physical examination concerning for Cushing’s syndrome, including many of the features depicted in the figure below (violaceous striae, dorsal fat pad, rounded facies, hypertension).

As a side note, a lot of medical terminology still used is out-of-date, insensitive, or offensive (including some listed in the figure below, which is adapted from an older text). Examples are ‘dowager’s hump’, ‘buffalo hump’, ‘moon face’, ‘incompetent cervix’, etc. I urge you to use objective plain-language terminology that is more respectful to patients, like ’rounded facies’, ‘dorsal fat pad’, etc.

Image adapted from ‘Netter’s Illustrated Human Pathology’ by L.M. Buja and G.R.F. Krueger, 2nd Ed., Saunders Elsevier 2014.

This patient underwent a 1mg Dexamethasone Suppression Test, Late Night Salivary Cortisol, and 24hr Urine Free Cortisol testing, all of which confirmed a diagnosis of Cushing’s syndrome.

The next question we asked was: WHY? To answer this, we went back to our two Golden Rules of Endocrinology:

1. Respect the axis (in this case, hypothalamus – pituitary – adrenal)
2. If it’s high, suppress it. If it’s low, stimulate it.

The Two Golden Rules of Endocrinology

I’ve summarized our approach to Cushing’s through the flowchart below, along with some investigation and treatment considerations:

3. Causes of ectopic ACTH production

In our case, further testing revealed that our patient had ACTH-Dependent Cushing’s with an 8-mg Dexamethasone Suppression Test that did not suppress, leading to a diagnosis of Ectopic ACTH production. In this case, we would go hunting for an ACTH-secreting tumour. These are rare, but some considerations include:

  • Bronchial carcinoid
  • Thymic carcinoid
  • Gastrinomas
  • Small cell lung cancer
  • Neuroendocrine tumours

4. A few other pearls

A few more key points to remember, both for real life and for your exams:

  • In a patient with rapidly progressing physical exam findings or progressive metabolic derangements (hyperglycemia, progressive hypertension, hypokalemia, metabolic alkalosis), have a high index of suspicion for hormonally active tumours.
  • In hypercortisolemic states, cortisol can have a greater degree of mineralocorticoid activity, which leads to hypokalemia and metabolic alkalosis.
  • Apart from pursuing the diagnostic pathways above, remember that patients with Cushing syndrome also need their usual preventative healthcare, including management of hypertension, diabetes or impaired glucose tolerance, dyslipidemia, osteoporosis, OSA, depression, NASH, and pregnancy/conception counselling.
  • Early referral to our endocrinology colleagues is key in the management of these patients!

Thanks to everyone who participated in this week’s Morning Report. I hope you found this post useful! Please email any questions or comments to cmr@wchospital.ca!

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