Sleep Disordered Breathing Interventions Improve Insomnia and Fatigue

TREATING CLINICIAN: Gavin Guard, PA

Patient Summary: Mark

• Overview Context: 
  • Mark is a 57-year-old male with a good diet, lifestyle, demeanor, and outlook, suffering from abdominal pain, insomnia, fatigue, and memory issues.

Visit 1 (Day 1) – History and Exam:

• Initial Symptoms:
  • Left abdominal pain (causing nighttime waking, typically around 4:30am)
  • Insomnia and fatigue 
  • Poor recovery from well-calibrated and reasonable workouts
  • “Pseudo-fibromyalgia” (mild aches and pains; body-wide, but focused on neck and feet)
  • Memory issues
  • Dizziness 
  • Belching

• Prior Diagnosis:  
  • Duodenal Ulcer, 2014 
  • Concussion, 1993

• Medications:
  • None

• Potential Abdominal Trauma
  • Lifelong wrestler, periods of pelvic pain

• Prior Testing Summary:
  • Mostly unremarkable other than TGF1 elevation

• Treatment History Summary:
  • Helpful
    • Probiotics (all 3 categories)
  • Non-Responsive
    • Elemental Diet (3 day)
    • Digestive Enzymes, HCl
    • Magnesium
    • Immunoglobulins 
  • Reactive
    • N/A

• Onset, Timeline and History:
  • Few illnesses and very few meds growing up. Always a light sleeper, but got worse after grad school.
  • “Intestinal virus,” a few times from age 26-29, where eating would cause moderate cramping. Incidences would last for weeks. Significant gas started during this period and lasted until his 40s.
  • Contracted toenail fungus in his 40s, which is still active.
  • Bought a home in 2003 and moved in. During that first year, the insomnia, waking with/from left abdominal pain started. Continued to present.

• Clinical Questions/Comments:
  • Is the history of worsening symptoms around the time of moving into a new house indicative of possible mold exposure? If so, should we address mold illness or start first with gut care?
  • I suspect his insomnia is at least partly attributed to suboptimal GI health. We also need to consider sleep disordered breathing. 
  • His history of wrestling could predispose him to chronic subacute pelvic trauma. Could pelvic floor dysfunction be contributing to his symptoms? 
  • Even though Mark has tried quite a few GI therapies with minimal response, there are other diets and higher levels of therapy that he has yet to explore. 

• Prognosis:
  • Good to excellent

Visit 2 (1 Week Later) – Clinical Decision Making, Testing and Initial Treatment Recommendations

• Differential Dx
  • SIBO
  • Dysbiosis
  • PI-IBS
  • GI-pain-driven insomnia
  • Sleep disordered breathing (snores lightly, had broken nose, single nostril breather)
  • Abdominal adhesions (lifelong wrestler, periods of pelvic pain)
  • Mycotoxicity (insomnia started when moving into new home, parents commented on musty smell)
  • Dietary mismatch (too low carb)
  • Fungal dysbiosis (toenail fungus, sore throat with high CHO)
  • Gastritis/ulcers (prev dx)
  • Supplement/food reactions causing insomnia 
  • GI pathogen 
  • EBV reactivation (sugars swell glands in neck, poor recovery, prior serology did not include EA)

• Recommended Testing
  • Trio-smart Glucose SIBO breath test (optional)
  • GI-Map stool test (optional)
  • ERMI dust test to assess mold in home or workplace 
  • CMP, CBC w/ differential, iron panel, vitamin D, lipids
  • Gastrin
  • Consider purchasing an Oura Ring to track sleep time and more importantly, monitor sleep quality: https://ouraring.com/

• Clinical Decision Making
  • Remember that lab testing is only ¼ of the data needed to make informed treatment decisions. In this case, we could forego lab testing, but since he has tried many foundational GI therapies, we will leave this as an option for him. 
  • A basic blood panel including iron status will uncover low-hanging fruit that we can address.

• Treatment Hierarchy 
  • Paleo low FODMAP diet, nighttime mouth taping, curcumin, fish oil, gut healing nutrients, probiotics, herbal antimicrobials
  • Mold testing, Dr. Burhenne (functional dentist), Oura Ring
  • Immunoglobulins retrial, Clear Passage referral (abdominal massage/treatment for adhesions), mycotoxin remediation and treatment
  • Hair health protocol
  • Increase carbohydrates, Fluconazole LD/longer term (for toenail fungus)
  • Complete supplement holiday, EBV treatment, HCl/Enzyme retrial 
  • Male hormone optimization

• Initial Treatment Recommendations
  • Diet and Lifestyle
    • Start on the Paleo Low FODMAP Diet. 
      • Do your best to be compliant, but you do not need to be perfect. 
    • Intermittent fast for 14-18 hours, 1-2 days per week.
      • This is just a general guide.  Experiment with longer and shorter windows to discover what works best. 
    • Meditate or perform breath work daily. While just one minute per day can help, studies show 20 minutes per day provides the most benefit. 
    • Start a practice of abdominal self-massage, see here for guidance.  
    • Sleep health 
      • Read The 8 Hour Sleep Paradox by Dr. Mark Burhenne 
      • Start tracking sleep with an Oura Ring – do this for 2-3 weeks to get a baseline before starting a practice of nightly mouth taping
  • NRT
    • EPA/DHA, Curcumin
      
      
  • GI
    • Probiotics: Lacto-Bifido, S. boulardii, Soil-Based
      
      
      
      
    • Gut healing nutrients
      
      
    • Herbal antimicrobials
      
      
      
      
      
  • Please be on the diet & lifestyle plan for 2 weeks before adding in the supplements. Then, continue diet, lifestyle & supplements until our follow-up. 
  • Be on the supplements for 3 weeks before following up 
  • Please make a note of the change you noticed from diet versus supplements 
  • Follow-up: 7-8 weeks

• Clinician Treatment Summary
  • We are starting to use self-abdominal massage earlier on in our treatment hierarchy for patients with abdominal pain or constipation. 
  • Gut healing nutrients for past history of duodenal ulcer.
  • Given the fact that he’s had a positive response to triple probiotics, I have a suspicion that he may have underlying dysbiosis that could benefit from an earlier utilization of antimicrobials. We can consider specific fungal antimicrobials later on, if necessary. 
  • You’ll notice that I’ve included some therapies later on in the hierarchy that he’s already tried with minimal response. In our experience, some patients can benefit from reintroducing therapies that historically they’ve been unresponsive to once they have laid a better foundation (e.g. better diet, triple probiotics, etc).
  • I had Mark perform some mouth taping as a mini-experiment to see if he could benefit from further sleep disordered breathing interventions. See our podcast with Dr. Zac Cupples with more information about treating sleep disordered breathing.

Visit 3 - Lab Interpretation and Treatment Evaluation

• Patient Self-Assessment 
  • Reports health as 80/100 and 5% better from when we began to work together
  • Nighttime waking and insomnia slightly improved 
  • Body aches and pains and recovery from workouts have stayed the same
  • Nothing has gotten worse
  • Abdominal self massage is helpful
  • Not sure about the mouth tape since it often comes off during the night
  • No response to paleo low FODMAP diet or intermittent fasting
  • Curcumin might be irritating
  • Took a bit to adjust to herbal antimicrobials, but then were tolerated well.
• Lab Results
  • TrioSmart Glucose Breath Test: Normal
  • GI-Map Stool Test:
    • H. pylori
    • Dysbiosis: 5 elevated 
    • Zonulin: 213
  • Labcorp Blood Work:
    • Total Cholesterol: 255 (H)
    • LDL-C: 170 (H)
    • Vitamin D, 25-Hydroxy: 43.8  
    • Gastrin: 16 pg/mL 
    • Ferritin: 303 ng/mL
  • Patient did not perform ERMI testing or purchase an Oura Ring.

• Lab Interpretation and Diagnosis
  • GI Map shows H. pylori, high zonulin and potential bacterial dysbiosis. Bloodwork shows high cholesterol and high-normal ferritin (possibly as a result of underlying inflammation).
  • Updated DDx
    • SIBO
    • Dysbiosis (dx 8/11 H. pylori) 
    • PI-IBS
    • GI-pain-driven insomnia
    • Sleep disordered breathing (Does snore lightly. Had broken nose, single nostril breather, mouth tape comes off at night)
    • Abdominal adhesions (lifelong wrestler, periods of pelvic pain)
    • Mycotoxicity (insomnia started when moving into new home, parents commented on musty smell)
    • Dietary mismatch (too low carb)
    • Fungal dysbiosis (toenail fungus, sore throat with high CHO)
    • Gastritis/ulcers (prev dx)
    • Supp/food rxns causing insomnia 
    • GI pathogen 
    • EBV reactivation (sugars swell glands in neck, poor recovery, prior serology did not include EA)

• Clinical Decision Making
  • We are on the right track (sometimes it can take a few weeks after herbal antimicrobials to see peak improvements), but I want to explore sleep disordered breathing since his mouth tape comes off at night (this can be a sign the patient has a hard time nasal breathing at night). I will suggest a WatchPAT ONE to screen for sleep disordered breathing.
  • Also adding NAC to protocol for sleep disordered breathing and H. pylori (research that NAC may help both). 
  • We will relax diet as well given that he was mostly unresponsive to dietary recommendations. There is no need to continue to restrict his food if we didn’t get a clear positive signal with initial suggestions. 
  • He is currently testing/remediating mold and this is something we can pursue if unresponsive to the next line of therapies. 

• Updated Treatment Recommendations
  • Diet and Lifestyle
    • Relaxed Paleo Diet 
    • Make a note of what your average Oura Ring sleep score is
    • Perform WatchPAT ONE home sleep test 
  • GI
    • Continue to 2nd month of herbal antimicrobials
    • NAC
      
      
  • Keep me posted on your ERMI test results.
  • Follow-up: 6-7 weeks

Visit 4 – Follow-up Visit and Treatment Evaluation

• Patient Self-Assessment 
  • Reports health as 80/100 and 5% better from when we began to work together, but maybe a little worse than last visit.
  • Fatigue, sleep quality, memory issues, and body aches/workout recovery all may have improved slightly, but hard to tell. Nighttime waking from abdominal pain is about the same, with the pain potentially a bit less.
  • Added vitamin D and collagen, in addition to prescribed supplements.
  • Indoor environmental professional wasn’t sure if mold was an issue. We will wait until next summer and see if he regresses.
• Clinical Decision Making
  • WatchPat One test showed mild obstructive sleep apnea and moderate desaturations.
  • Some patients may see peak improvement of symptoms a few weeks after ending the herbal antimicrobials. This could be from the transient irritation they cause in the GI tract. Just because he hasn’t seen substantial improvement with these, it doesn’t mean they are not working. We will monitor his response with this time frame in mind. 
  • Today we will start myofunctional therapy, oxygen tracking, and retesting H. pylori before our next follow-up. At the clinic, we are utilizing myofunctional therapy +/- respiratory training before mandibular advancement devices in most patients with mild to moderate sleep apnea given the possible long-term adverse effects of the latter. We will track his desaturations using a Wellue02 oximeter tracking ring for ongoing surveillance.
  • This might be all that is needed – if not, we can continue GI work.

• Testing Recommendations
  • Retest stool 3 weeks prior to next visit 
  • Keep me posted on your ERMI test results

• Updated Treatment Recommendations
  • Lifestyle
    • Start myofunctional therapy with Janett at Ashville Speech
    • Stop the nightly mouth taping for now – we will revisit after the myofunctional therapy  
    • Track sleep with Wellue02 oximeter tracking ring
  • Follow-up: 6-8 weeks

Visit 5 – Lab Interpretation and Treatment Evaluation (as needed)

• Patient Self-Assessment 
  • Reports health as 85/100.
  • Night waking, abdominal pain, fatigue, and body aches all improved. 
    • Reports having “more ‘spring’ in my body. Recovery seems subtly more ‘typical’.”
  • Memory and struggling to find words are the same.

• Lab Results
  • Sleep has not shifted notably 5 weeks into tracking
  • GI-MAP:
    • H. pylori detected, not positive. No virulence. 
    • Dysbiosis: 3 elevated

• Lab Interpretation and Diagnosis
  • Lower dysbiosis and no more H. pylori after probiotics and herbal antimicrobials. 
  • Presence of H. pylori on a GI Map that does not flag as high is not a problem in our opinion. There is no need for further interventions to treat this finding. 
• Clinical Decision Making
  • Either the myofunctional therapy or the herbal antimicrobials (even months after ending them) have improved sleep, pain, and energy levels. I believe we can continue on our current track to see what further improvements we can achieve.

• Updated DDx
  • SIBO (r/o 8/11)
  • Dysbiosis (dx 8/11 H. pylori, now negative) 
  • PI-IBS
  • GI-pain-driven insomnia
  • Sleep disordered breathing (dx 9/29)
  • Abdominal adhesions (lifelong wrestler, periods of pelvic pain)
  • Mycotoxicity (IEP wasn’t sure if this was a problem)
  • Dietary mismatch (too low carb)
  • Fungal dysbiosis (toenail fungus, sore throat with high CHO)
  • Gastritis/ulcers (prev dx)
  • Supp/food rxns causing insomnia 
  • GI pathogen (r/o GI-Map)
  • EBV reactivation (sugars swell glands in neck, poor recovery, prior serology did not include EA)

• Updated Treatment Recommendations
  • Maintain the current plan. Repeat the WatchPAT ONE 2-3 weeks before our next visit, and the mouth taping.
  • Follow-up: 6-8 weeks

Clinical Rule(s) and Final Clinician Comments

• Clinical Rule: Address underlying GI dysfunction before beginning testing or treatment for environmental toxicity including mycotoxicity, heavy metal toxicity, as well as chronic infections.
  • In Mark’s case, he flagged for possible mold exposure, but it turned out not to be a major contributing factor after an evaluation by an IEP. He benefited mostly from GI and sleep-focused care.
  • If a patient expresses a clear history of mold exposure, you may offer mold testing to help guide treatment after laying the foundations of diet, lifestyle, and basic GI support. 
  • All 3 categories of probiotics have shown benefit in reducing mycotoxicity and should be encouraged even in the presence of mold/candida colonization. 
• Clinical Rule: In those with refractory fatigue, insomnia, and/or chronic pain, consider sleep disordered breathing. 
  • Mark was minimally responsive to foundational diet, lifestyle, and GI care, but benefited from myofunctional therapy and mouth taping.

Questionable Autoimmune Diagnosis Resolved with Gut-targeted Care

Patient Summary: Jim

• Overview Context: 
  • Jim is a 59-year-old male with a good outlook and demeanor, with a suboptimal diet and lifestyle who is seeking answers for myalgia, fatigue, and headaches that started 2 months ago w/ insidious onset.
  • He is fairly concerned about a possible diagnosis of polymyalgia rheumatica (from a primary care doctor) and would like a diagnosis for his symptoms.
• Concerns and Goals
  • Jim would like to uncover the underlying cause(s) of his symptoms and resolve the headaches, muscle aches, and intense fatigue that has progressed over the last 2 months. He also would like to improve symptoms of reflux and constipation that have been present over the last few decades.

Visit 1 (Day 1) – History and Exam:

• Initial Symptoms:
  • Headache, constant and severe
  • Muscle aches, intermittent upon exertion
  • Fatigue, accompanies muscle aches
  • Other symptoms:
    • Reflux
    • Constipation, bowel movement every other day w/ straining
    • Sensation loss in fingers

• Prior Diagnosis:  
  • GERD, 30 years ago
  • Migraines, last 30 years

• Medications:
  • Meloxicam, for  headache
  • Omeprazole, 10mg every other day
  • Long-term use of NSAIDs for migraines
  • Prednisone, 5 day course by PCP

• Prior Surgical History (if relevant)
  • 2015 – hernia mesh repair
  • 2020 – oral implants

• Prior Testing Summary:
  • 2021 CT scan – unremarkable

• Treatment History Summary:
  • No diets tried 
    • Current diet: mostly processed foods
  • Prednisone – helped fatigue, myalgia
  • Has not tried any GI therapies

• Onset, Timeline and History:
  • 50+ years as a painter with minimal personal protective equipment
  • All symptoms started 2 months ago with acute onset
  • No known preceding triggers or events prior to onset
  • PCP thought it was polymyalgia rheumatica and prescribed ketorolac, meloxicam, prednisone with only some alleviation of all symptoms
    • BUT, symptoms quickly returned when done w/ course of prednisone

• Clinical Questions/Comments:
  • Will refining a clear diagnosis for his symptoms improve his care? Or, can we work through empirical trials of various therapies in a stepwise fashion?
  • Is extensive testing necessary to inform care?
  • I suspect his GI system is a large contributing factor to his symptoms given his long-term history of NSAIDs and surgical history.
  • Will also address sleep disordered breathing, abdominal adhesions, and toxic burden if non-responsive to GI-focused care.

• Prognosis:
  • Good-excellent given lack of GI care and a lot of room for improvement regarding diet/lifestyle 

Visit 2 (1 Week Later) – Clinical Decision Making, Testing and Initial Treatment Recommendations

• Differential Dx
  • Dietary & Lifestyle 
    • Dietary mismatch (SAD, FODMAP, Histamine)
    • Sedentarism (lack of formal exercise)
    • Poor sleep hygiene, timing, or duration (6-7 hrs sleep)
    • High allostatic load (work, lack of support from wife)
    • Lack of purpose
    • Social isolation (stress from wife)
  • Gastrointestinal
    • Dysbiosis
    • Gastritis (NSAID everyday, reflux)
    • Hypochlorhydria
    • Histamine intolerant (migraines, reflux)
    • GI pathogen
  • Hormonal
    • Andropausal-male
    • Hypothyroid
  • Nutritional 
    • Iron overload 
    • Nutritional Deficiencies 
  • Autoimmune Phenomena
    • Polymyalgia rheumatica (myalgia, fatigue, headache)
  • Other/2nd level 
    • Sleep disordered breathing (fatigue, brain fog)
    • Abdominal/pelvic adhesions (umbilical hernia mesh)
    • MCAS
    • Oral health imbalance (implants)
    • Heavy metal toxicity (painter since 7 yo)

• Recommended Testing
  • Standard blood panel: CMP, CBC w/ diff, ferritin, Vit D
  • Additional markers: TSH, hs-CRP, B12
  • AVISE autoimmune panel

• Clinical Decision Making
  • Ruling out anemia with ferritin, CBC, B12
  • CRP to assess for possibility of polymyalgia rheumatica given that 99% of PMR cases have elevated CRP (X)
  • TSH for hypothyroidism screen 
  • AVISE autoimmune panel will likely NOT inform care. However, the patient desired to have more testing to refine possible diagnosis. This test is covered by insurance and will NOT be a financial burden.

• Treatment Hierarchy 
  • Relaxed paleo. Partial elemental diet. No food 1-2 hrs before bed. Hydration.  
  • Three categories of probiotics. Gut healing nutrients. Paleo low FODMAP.
  • Vit D., Herbal antimicrobials + magnesium. Sleep disordered breathing. 
  • Immunoglobulins. Low Histamine diet. 
  • Heavy metals/detox

• Initial Treatment Recommendations
  • Diet and Lifestyle
    • Relaxed paleo template
    • No food 1-2 hrs before bed
    • Adequate hydration
  • GI
    • Partial elemental diet (replace 1-2 meals per day)
  • Follow-up: 3 weeks

• Clinician Treatment Summary
  • I am NOT particularly concerned about obtaining a clear diagnosis with Jim. Why? Because this will likely minimally affect my treatment plan of empirical trials of therapies. However, I considered patient preference and ordered an autoimmune panel. Remember, lab testing is ¼ of the data necessary to make a clinical decision.
  • Given his suboptimal diet and lifestyle, we will begin with the fundamentals (e.g. relaxed paleo) before adding more complicated therapies. I also suspect he will have a hard time implementing a more restricted diet given his demeanor and history.

Visit 3 - Lab Interpretation and Treatment Evaluation

• Patient Self-Assessment 
  • Myalgia – 75% better
  • Headache – 50% better
  • Reflux – resolved
    • Relaxed paleo template and not eating 1-2 hrs before bed helped
  • Has not had to take Meloxicam or PPI since implementing these changes. 
  • He would like to adjust his choice of liquids, but has a hard time drinking straight water.

• Lab Results
  • Ferritin – 167
  • Hemoglobin – 14
  • Vit D – 30 
  • B12 – 1,200
  • TSH 1.5, TPO Abs <4 
  • CRP – 2.6
  • AVISE panel unremarkable other than positive ANA titer (1:160) and weak positivity for anti-cardiolipin IgG 
    • No other positive antibodies suggesting antiphospholipid syndrome

• Lab Interpretation and Diagnosis
  • Testing mostly unremarkable
  • Jim could be part of the population w/ ANA positivity without a true autoimmune disease diagnosis.
  • Since 99% of those w/ PMR have CRP >5 mg/L, this makes this diagnosis less likely.

• Clinical Decision Making
  • We could continue with the current plan given his remarkable improvement. However, Jim seeks to do more. We will continue with more foundational GI care.
  • Will also add in some electrolytes to help with hydration.

• Updated Treatment Recommendations
  • GI
    • S. boulardii, Soil-Based, and Lacto-Bifido blend probiotics
      
      
      
      
    • Gut healing nutrients
      
      
  • NRT
    • Electrolytes
      
      
  • Follow-up: 6-8 weeks

Visit 4 (4 Weeks Later) – Patient Correspondence

• Patient Self-Assessment 
  • Patient messaged me to inform me of a new symptom of food getting stuck in the esophagus when eating. 
  • He attributes this to starting the new supplements (triple probiotics and gut healing nutrients) which he began 3 weeks ago. These symptoms started 2 weeks ago.

• Clinical Decision Making
  • Is this from stopping the PPI too soon or a true adverse reaction to the supplements? Given that probiotics can often improve dyspeptic symptoms, I suspect it’s more of the former. However, in order to truly tell, we will perform a mini-trial of discontinuation and reintroduction.

• Updated Treatment Recommendations
  • Stop all the new supplements, wait until symptoms get better and add them back in one at a time (for 1-3 days before adding another one) to see if there’s a particular one that is the problem.
  • In the meantime, I’d suggest doubling down on the elemental diet shake and consider using it for 2 of your meals (instead of 1).
  • Follow-up: As scheduled in 4 weeks

Clinical Rules and Final Clinician Comments

• Clinical Rule: Start with the least invasive treatments first – gut, diet and lifestyle. 
  • Jim responded very well to foundational diet and GI care. There was not a need to speculate as to the mechanisms behind his symptoms. Rather, we worked through an organized list of therapies that corresponded to his differential diagnosis, while documenting the signal to therapies utilized. 
• Clinical Rule: Exhaust low-risk, empirically-informed treatments prior to the consideration of testing to guide/modify treatment recommendations.
  • We could have easily pursued extensive testing for Jim given his willingness and desire to get down to the root cause(s) of his severe symptoms. However, this was unnecessary and could have possibly distracted us from utilizing the therapies that helped. Furthermore, waiting on these test results could have delayed us from getting him better. 
  • Nailing down a clear diagnosis is NOT always necessary. In this case, the patient (and PCP) were convinced that he had polymyalgia rheumatica, but labs suggested otherwise. Nonetheless, these test results did NOT really change care all that much.

We are now working through deciphering the nature of his new symptom of dysphagia. I suspect this is more a result of stopping the PPI too early, but we will adjust as necessary. I anticipate that he will not need much more care to reach his health goals. 

Can Subclinical Hypothyroidism Correct on Its Own?

Clinical Question

• What is the rate of those with subclinical hypothyroidism (SCH) who are euthyroid on follow-up without treatment?

Functional Medicine “Bias”

• A common practice in functional medicine is to treat all thyroid dysfunction outside “optimal ranges.” This includes giving thyroid replacement therapy for those with subclinical hypothyroidism (high TSH, normal fT4).

What Does The Evidence Actually Suggest?

• Up to 74% with SCH will become euthyroid on follow-up without treatment. 

What Should I Do In Clinical Practice?

• If a patient is hypothyroid, consider follow-up testing in 2-3 months while addressing diet, lifestyle, and GI health before treating with thyroid replacement therapy. 

Primary Study Title

• Transient high thyroid stimulating hormone and hypothyroidism incidence during follow-up of subclinical hypothyroidism
  • https://pubmed.ncbi.nlm.nih.gov/34879182/

Intervention Details

• Prospective study of 431 healthy control participants, 225 patients with SCH
• Tested thyroid status before and after 6 month follow-up
• No treatment was given to either group

Study Author’s Primary Conclusion

• Of those w/ baseline SCH, at a 6 month follow-up:
  • 12.2% developed frank hypothyroidism
  • 13.4% stayed SCH
  • 73.8% became euthyroid
• TPO antibodies and a TSH above 6.9 mIU/L was associated with a higher risk of developing overt hypothyroidism.
  • “The incidence of overt hypothyroidism for participants with TSH above 6.9 mIU/L was 36.7%. For female participants, incidence of overt hypothyroidism was 16.1%, while it was 42.3% for female participants with TSH at baseline level above 6.9 mIU/L.”

Interesting Notes

• According to last month’s FFMR research review, consider treating SCH in the following scenarios:
  • Younger (<70 yo), TSH between 7-10
  • Older (>70 yo), TSH between 7-10 with significant symptoms
  • TSH >10 regardless of age
• This last narrative review also noted the importance of retesting the TSH before treating. In another study referenced, 62% of those with SCH became euthyroid without treatment.
  • “Before diagnosing and treating subclinical hypothyroidism, one must ascertain whether steady-state conditions exist, and whether hypothyroidism is transient. Transient TSH elevation can be seen during recovery from nonthyroidal illness, and transient hypothyroidism may occur following destructive thyroiditis (painless, postpartum, granulomatous, or drug induced).”
  • “Additionally, TSH is released in pulses, which becomes more frequent in the evening; TSH sampled at the time of a pulse might transiently be just above the upper limit of normal, especially in a patient whose baseline TSH levels are in the upper portion of the normal range.”
  • “A study from an HMO database illustrates the importance of obtaining two TSH levels before considering treatment. Among over 422,000 patients, none of these patients were on thyroid medications, 3% had an elevated TSH; when lab tests were repeated, 62% became normal spontaneously.
  • “The European Thyroid Association guideline for management of subclinical hypothyroidism recommends a repeat TSH measurement preferably after a 2–3-month interval.”
• In a randomized, double-blind crossover study of 341 participants (X), 8% of those w/ SCH were given either Levothyroxine (to achieve TSH level of 0.6-2.0 mIU/L) or placebo, and then crossed over to the other group for four months each. There was no difference in symptoms between the two groups if the repeat TSH was <4.5 mU/L. 

Secondary Study Title

• Treating hypothyroidism is not always easy: When to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy:
  • https://onlinelibrary.wiley.com/doi/10.1111/joim.13410
• A randomized double-blind crossover trial to investigate the efficacy of screening for adult hypothyroidism:
  • https://pubmed.ncbi.nlm.nih.gov/21258125/

Final Comments

The vast majority of those who were SCH became euthyroid WITHOUT treatment. This is a great study showing us that many times SCH will correct on its own. Also addressing gut health will most likely improve the rate of those who become euthyroid. There is no need to rush treating SCH in the majority of cases. Consider retesting thyroid function levels in 2-3 months.

What’s Better: Generic or Brand Levothyroxine?

Clinical Question

• Is brand name Synthroid better than generic levothyroxine for those with hypothyroidism?

Functional Medicine “Bias”

• Some speculate that brand name Levothyroxine (Synthroid) is superior to generic levothyroxine for treating hypothyroidism. 

What Does The Evidence Actually Suggest?

• Brand levothyroxine (Synthroid) results in a minor 1.3% difference in those who achieve optimal TSH targets.
• However, this may not be clinically relevant.

What Should I Do In Clinical Practice?

• Given the lack of meaningful, clinically significant difference between those who received brand vs generic levothyroxine, we speculate that it probably does not matter what kind of levothyroxine you use. 
• Use the Thyroid Treatment Algorithm to achieve a TSH that is in the normal range. 

Primary Study Title

• Comparative Effectiveness of Persistent Use of a Name-Brand Levothyroxine (Synthroid®) vs. Persistent Use of Generic Levothyroxine on TSH Goal Achievement: A Retrospective Study Among Patients with Hypothyroidism in a Managed Care Setting:
  • https://pubmed.ncbi.nlm.nih.gov/34905150/

Intervention Details

• Retrospective study of 36,764 patients with hypothyroidism 
  • 18,382 on Synthroid 
  • 18,382 on generic levothyroxine

Study Author’s Primary Conclusion

• At 12 month follow-up:
  • Significantly more patients receiving Synthroid were in the TSH reference range vs. general levothyroxine
    • “Mean TSH level was 2.4 mIU/L in the Synthroid cohort and 2.6 mIU/L in the generic levothyroxine cohort (p <0.001).
    • “The proportion of patients achieving TSH levels within the goal range was significantly higher in the Synthroid cohort compared with the GL cohort (78.5% vs. 77.2%, respectively, p = 0.002).”
  • Synthroid was still slightly better even when using a narrower TSH range
    • “These results remained consistent when a narrower TSH range (0.4–4.0 mIU/L, as suggested in the 2014 ATA guidelines [6]) was applied: 75.2% of patients in the Synthroid cohort and 73.9% in the generic levothyroxine cohort had TSH levels within the narrower range (p = 0.003).”
  • Both groups had similar healthcare costs and provider visits
    • “Health care related utilization and costs were broadly similar between the cohorts in terms of all-cause inpatient hospitalizations, emergency department visits, outpatient services, and pharmacy fills.”
  • Patients with normal TSH had the best outcomes
    • “Irrespective of index medication, patients with TSH within the reference range had significantly lower hypothyroidism-related medical and total costs compared to those outside the range.”
• The authors suggest:
  • “Given that levothyroxine is one of the most commonly prescribed drugs in the US, with use rates between 5 and 7% of adults [15] (an estimated 15 m users in 2021), the absolute difference of 1.3 percentage points may translate into tens of thousands of patients with suboptimal outcomes.”

Additional References and Reviews

• Thyroid Treatment Algorithm

Final Comments

• Since this was such a large study, they were able to detect a statistically significant difference between the two groups. Even though these results are statistically significant, we argue that they are not clinically significant (only a 1.3% difference). On a population level, it may make a difference. However, on an individual basis, dose and type of thyroid replacement should be individualized per the Thyroid Treatment Algorithm.
• We argue that it doesn’t matter if you use Synthroid or generic levothyroxine – just get a hypothyroid patient’s TSH level in the normal range and optimize their GI health.

Practitioner Tip

How aggressive should you be with your treatment recommendations?

How should you gauge how conservative or aggressive to be with treating patients? Here are a few factors to help you decide on the intensity/amount of interventions you should use. 

1. Severity of symptoms: Patients with more severe symptoms will often require a more aggressive line of therapy. For example, a patient with IBD who is having 7 watery stools per day and quickly losing weight will require more interventions than an IBD patient who just wants to maintain health. 
2. Prior treatment history and response: Consider how many therapies the patient has tried and to what degree they’ve helped/not helped. A patient who has not done much to improve their health will often require less than someone who has tried many therapies with minimal response. 
3. Current diet and lifestyle practices: If a patient is following a poor diet, not exercising, and/or is getting inadequate sleep, then revisit these foundations before moving to more exotic therapies. 
4. Patient demeanor and attitude: Take into account the patient’s perspective, willingness, readiness, and ability to follow through with your recommendations. A working mother of 4 may have less bandwidth than a single bachelor to incorporate your recommendations. 

Keep the above in mind when considering how heavy-handed you should be when treating patients.