8/10 PPMC Report: Secondary Amenorrhea

Today we discussed the case of a 31 yo F with PMH of ?PCOS presenting with difficulty conceiving after attempting for 3 years.

First of all — the PPMC report team agreed that three years was too long! She should be referred for work up after 1 year (or 6 months if >35yo) of attempting to conceive (sex ~2x weekly) without resultant pregnancy.

We discussed the Rotterdam criteria to diagnose PCOS (2003).

Two out of three of the below:

  1. Oligo/anovulation
  2. Clinical/biochemical signs of hyperandrogenism
  3. Polycystic ovaries on US (>12 follicles)

WITHOUT other causes of hyperandrogenism present.

We reviewed the other causes of hyperandrogenism (…and when to go looking for them) including tumor (ovarian/adrenal), congenital adrenal hyperplasia, Cushing’s disease and acromegaly.

Amenorrhea

Following the above workup algorithm, our patient had hypogonadotropic hypogonadism and an MRI which demonstrated a pituitary mass. Given her presentation with hyperandrogenism, the PPMC report team went back and ordered a Cushing’s and Acromegaly work up which demonstrated elevated IGF-1 which did not suppress with a glucose load — diagnosing this patient with acromegaly 2/2 a hyperfunctioning pituitary adenoma!

7/24 (HUP): thyroid physiology and amiodarone-induced thyroiditis

Thanks to Dr. Caitlin White for guiding us through the case of an elderly man with aortic stenosis and atrial fibrillation who was found to have amiodarone-induced thyrotoxicosis.

First, a framework for hyperthyroidism. Causes of hyperthyroidism can be divided into those that lead to:

A) autonomous thyroid hormone production (hot nodule, Graves, etc): increased uptake on radioactive iodine uptake scan (I123)
B) destructive thyroiditis (leading to leakage into the bloodstream of stored thyroid hormone- Hashimoto’s, viral, amiodarone, etc): no uptake on I123 scan
C) Extrinsic thyroid hormone production: struma ovarii, exogenous thyroid hormone intake, etc

An important bit of physiology to know if you want to understand the thyroid:

The thyroid produces T4 (and T3) in a 14:1 ratio, but mostly T4 is deiodinated in the periphery into the biologically active T3.

Wolff-Chaikoff effect: the thyroid is tightly autoregulated so that it doesn’t suddenly produce a huge amount of thyroid hormone just because of swings in your dietary iodine intake (ex: seafood). Thus, the Wolf-Chaikoff effect is characterized by a transient stoppage in thyroid hormone synthesis after a high iodine load. Your thyroid ‘escapes’ from this in 1-2 weeks and returns to normal.

Jod-Basedow phenomenon: in a thyroid with underlying autonomous thyroid hormone production (Graves, toxic multinodular goiter), normal regulatory mechanisms (ie the Wolf-Chaikoff effect, above) are bypassed, and the autonomous thyroid overproduces thyroid hormone possibly leading to hyperthyroidism. This can happen after an iodinated contrast load…or amiodarone exposure, for example.

Amiodarone-induced thyroid dysfunction

An average normal iodine intake for an adult is 0.2-0.3 mg/day. In contrast, one 200mg dose of amiodarone has 6mg of iodine (about 30x the dietary intake!). Amiodarone is lipophilic and can be slowly released from fat stores long after the drug is stopped, meaning thyroid dysfunction can occur even if you’re not on the drug.

Patients can get either hypothyroidism or hyperthyroidism from amiodarone. It is idiosyncratic, and the risk of its effect on the thyroid cannot be predicted based on how long the person has been taking amiodarone (ie you can run into thyroid issues at any time).

There are two flavors of amiodarone-induced thyroiditis (AIT):

Type I AIT: characterized by increased T4 and T3 production, usually due to pre-existing ‘thyroid autonomy’, ie Graves’ disease or toxic nodule which uses the amio/iodine load to churn out more thyroid hormone.
Rx: methimazole (preferred; risk of agranulocytosis) or PTU (less preferred except in 1st trimester pregnancy, due to risk of liver failure). Stop amiodarone.

Type II AIT: caused by direct destructive effect of amiodarone on the thyroid, leading to a destructive thyroiditis. In this case, hyperthyroidism is caused by leakage of stored thyroid hormone into the bloodstream (not increased synthesis, as in type II). Most common in the US.
Rx: prednisone. Stop amiodarone.

You can continue amiodarone in patients with amiodarone-induced hypothyroidism (but not hyperthyroid).

 

A few other thyroid pearls

Suspicious of thyroid pathology? Start with a TSH. If normal, the only reason to get T4/T3 is concerned for pituitary pathology or critical illness- otherwise, you’re done.

  • TSH high: check a total T4 +/- free T4 (a calculated assay that supposedly accounts of protein binding abnormalities but doesn’t always do so perfectly).
  • TSH low: check both total T4 and T3.

 

NB: you’ll sometimes see patients come in on Armour- or Nature thyroid, which is dessicated pig thyroid. The problem is that pig thyroid has a T4:T3 ratio of 4:1, so there’s much more T3 than the human thyroid (14:1 ratio); since T3 is the biologically active hormone, there’s a higher risk of hyperthyroid symptoms.

Common thyroid function derangements

TSH T4 T3 Abnormality
Primary hypothyroid
TSH secreting adenoma
NORMAL ↑TBG from estrogen (preg, OCP); thyroid hormone resistance
NORMAL Subclinical hypothyroidism; recovery from nonthyroidal illness; HAMA
↑↑ Thyrotoxicosis
NORMAL NORMAL OR ↓ Subclinical hyperthyroidism; nonthyroidal illness; exogenous meds (dopamine, steroids)
Central hypothyroidism

References

  1. Loh, K.-C. 2000. Amiodarone-induced thyroid disorders: a clinical review. Postgraduate Medical Journal. PMC1741517

 

7/10 PPMC Report: DM Foot Ulcers

Today Tariq presented a fascinating case of a gentleman with neuropathy and c/f gas gangrene of his right foot.

This lead us on to a discussion about diabetic foot ulcers and a new perspective/respect for what they mean for our patients.

PEARLS:

  1. DM foot ulcer infections are POLYMICROBIAL – so keep things broad!
  2. The risk of death at 5 years for a patient with a diabetic foot ulcer is 2.5x as high as the risk for a patient with DM who does NOT have a foot ulcer. (1)
  3. Mortality after a DM-related amputation exceeds 70% at 5 years for all patients with diabetes. (1)

Take a glance over the NEJM article I was quoting from during report (and here) for a GREAT summary!

References:

  1. Armstrong DG, Boulton AJM, Bus SA. “Diabetic Foot Ulcers and Their Recurrence.” NEJM 2017;376:2367-75. http://www.nejm.org/doi/full/10.1056/NEJMra1615439

7/5 PPMC Report: Adrenal Insufficiency

Today we discussed a case of autoimmune primary adrenal insufficiency presenting in a 24 yo F as N/V, hypotension and hyponatremia.
PEARLS For evaluation of HYPONATREMIA: 
HypoNa
1. Useful to get Serum Osm (and calculate your own!), UOsm, UNa.
2. The VOLUME STATUS EXAM is crucial! While many “classic” physical exam findings associated with hypovolemia are not useful in isolation, in summation they are likely much better. Remember to check for axillary sweat (+LR 2.8, -LR 0.6, sensitivity 50%, specificity 82%).(1)
For ADRENAL INSUFFICIENCY:
1. If suspected don’t be afraid to give a dose of hydrocortisone early! It lasts approximately 24 hours, so try to draw a random cortisol level/ACTH, Aldo/Renin level ahead of time. The crisis level dosing of hydrocort (100-200mg) should provide enough mineralocorticoid activity that you don’t need to think about adding fludrocort.
2. You can do a cosyntropin test ANYTIME — no need to wait for a specific time of day. Two cortisol/ACTH measurements (a baseline and 60 minutes after administration) are all you really need. THE PENN LAB HAS DIFFERENT CUT OFF POINTS FOR NORMAL THAN OTHER LABORATORIES — so check your “normal” ranges closely.
3. To confirm diagnosis of autoimmune send of “adrenal antibodies” in PennChart. Patients should likely get CT A/P to evaluate for adrenal hemorrhage, granulomatous disease, metastases, and an infectious work up.
4. Patients with primary adrenal insufficency should be maintained on hydrocort and fludrocort as outpatients. They need to DOUBLE or even TRIPLE their meds when they get a cold/ill for any reason. We do NOT trend ACTH in these patients, we treat based on symptoms!
5. There are tons of risk factors that put you at higher risk for adrenal insufficiency (2) is an excellent short read if you want to learn a bit more!
References:
1. McGee S, Abernethy WB, Simel DL. The rational clinical examination. Is this patient hypovolemic? JAMA. 1999 Mar 17;281(11):1022-9.
2. Bornstein, SR. Predisposing Factors for Adrenal Insufficiency. NEJM. 2009;360;2328-39.