A man in his late 30s came to me with a goal he phrased in two parts: “work on my immunity” and “work on my autoimmune disorders.” The plural was what caught my attention.

Three months earlier he had been in the ER with a fasting glucose above 300 and a three-week flu-like illness with swollen neck nodes. The node biopsy came back as Kikuchi-Fujimoto disease, a rare necrotizing lymphadenitis that is itself linked to autoimmunity. He left on insulin glargine and metformin. He had also been on levothyroxine 200 mcg for six or seven years, and he was not sure anyone had ever checked his thyroid antibodies. Add a history of evening rashes on his legs, energy levels of 5/10, heavy work travel, roughly two drinks a night, and a family history of diabetes and heart disease.

His chart held a hypothyroid label, a diabetes label, and a rare lymph node diagnosis, each managed and evaluated separately. I was less interested in any single label than in whether one immune system was producing all of them.

Top Three Patient Goals

• Calm the immune system and lower his autoimmune antibody burden
• Get off as much diabetes medication as safely possible
• Restore energy, strength, and resilience through heavy work travel

Why I Started with Foundations

Autoimmune disease rarely travels alone. Roughly 25 percent of people with one autoimmune disease are estimated to develop another, and some cohorts report higher rates¹. The pairing of thyroid and gastric autoimmunity is especially well documented. In one review, about 40 percent of patients with autoimmune thyroid disease had atrophic body gastritis and 16 percent had pernicious anemia².

This changes what a good first visit looks like. If the odds of a second condition are that high, you should screen for it deliberately instead of waiting for it to announce itself. You also look at the shared soil those conditions grow in: nutrient status, gut integrity, glycemic control, chronic infection, stress physiology, and sleep. In functional medicine we call these the foundations. We work on them first because they are modifiable, they are measurable, and they influence how the immune system behaves regardless of which organ it happens to be attacking.

My first round of testing covered a very broad blood panel (CBC, CMP, A1c, insulin, lipids and inflammation markers, a full thyroid panel with antibodies, B12, folate, homocysteine, methylmalonic acid, vitamin D, zinc, copper, magnesium, iron studies and more), stool testing, SIBO breath testing and the Cyrex Array 3X wheat and gluten reactivity panel (now called Cyrex WheatBurden).

What the First Labs Showed

The thyroid panel stopped me in my tracks. His TSH was below 0.01 with a free T4 of 4.8 and free T3 at 3.0. He was not hypothyroid on paper anymore. He was even potentially over-replaced on T4 hormone, and I asked him to take the results to his prescribing physician for a dose reduction. His TPO antibody was 884 and thyroglobulin antibody 523. This was Hashimoto’s, confirmed for the first time.

The nutrient picture was the second surprise. B12 was 168 pg/mL, and 25-OH vitamin D was 10 ng/mL. Zinc was low at 64, with a zinc-to-copper ratio of 0.68. Hemoglobin was 12.9 with an MCV of 78 and a low MCH, yet his ferritin was 326 and his hs-CRP was 2.7.

Those last values did not agree with each other. A microcytic picture alongside a high ferritin made me question the ferritin. Ferritin is an acute phase reactant, so inflammation can inflate it and hide a true iron deficiency. I followed this up with a soluble transferrin receptor, which is less affected by inflammation. Low B12 with microcytic indices also raised the possibility of a mixed picture, where an iron-restricted process masks the macrocytosis you would expect.

His A1c was 6.3 with medication treatment, uric acid 9.4, and AST and ALT 37 and 45 after the glucose crisis, with a fatty liver on prior imaging. And his Cyrex Array Wheat Burden came back strongly positive.

What the Wheat Panel Added

His Cyrex Array 3X (now called the Wheat Burden test) was strongly positive across the board: whole wheat, multiple gluten peptides, wheat germ agglutinin, non-gluten wheat proteins, and microbial transglutaminase, the protein-binding enzyme used in many processed foods. The tissue transglutaminase markers tied to celiac disease were all in range, and celiac genetics later came back negative. This was a non-celiac wheat and gluten sensitivity³, and in a man already carrying two autoimmune diagnoses, it meant a daily source of immune stimulation at the gut lining, the same lining his vitamin D, zinc, and iron depended on. A standard celiac screen would have missed it entirely.

The Question Behind the Low B12

A B12 of 168 in a man eating a normal diet needs more digging. First we review his diet intake to ensure there aren’t any red flags for low intake of Vitamin B12, then consider any issues that might be happening with absorption and utilization of the nutrient. I ordered intrinsic factor blocking antibody, parietal cell antibody, and gastrin. Intrinsic factor and parietal cell antibodies tell you whether the stomach is under immune attack. Gastrin matters because it should be normal or elevated in autoimmune gastritis, and a very high level raises a different question, namely a gastrin-secreting tumor.

The intrinsic factor antibody was positive, the parietal cell antibody was elevated at 53.7, and gastrin was normal. Pernicious anemia, the second autoimmune disease, now had a name. This overlap is well described: autoimmune thyroid disease is among the most common associations of pernicious anemia, and the two share a common autoimmune predisposition².

Typically oral B12 is an unreliable plan when intrinsic factor is blocked (although I do find sublingual B12 lozenges to work really well in this situation but of course deciding best course of action should also depend on how low the levels are and how fast you need to get them back to therapeutic levels), so he started intramuscular B12 twice weekly and tapered to a maintenance interval. After injections, serum B12 stops being informative because the number will be sky-high. I followed homocysteine instead. It fell from 11.8 into the 7 to 8 range as his injections settled. His methylmalonic acid ran low throughout and never fit the usual pattern

Type 1 or Type 2?

His diabetes got the same scrutiny. A man with a glucose over 300 during an immune flare, with a rare lymphadenitis and thyroid autoimmunity, deserved GAD65, IA-2, ZnT8, and islet cell antibody testing before anyone assumed type 2. All were negative. Over the first year his insulin and metformin were withdrawn and he focused mostly on lifestyle adjustments, dietary changes, supplements, etc., and his A1c settled in the low 6s and then to 5.8. I suspect his hyperglycemia was substantially driven by the immune and stress surge around the Kikuchi episode. Over the years, he eventually did get put on Mounjaro to help with weight and further blood sugar control, which has improved numbers even more. 

The Diet, in Sequence

His reactivity array justified a strict gluten-free diet, and because his panel reached non-gluten wheat proteins and microbial transglutaminase, that meant all wheat, not only gluten, and far fewer processed foods. On top of that I built a time-restricted ketogenic pattern with a glucometer carbohydrate challenge first, because a man recently on insulin should not have his diet restructured blind. Protein stayed high throughout to protect lean mass while his glucose came down.

Stool Testing and the Infection That Would Not Leave

His stool testing showed H. pylori, markedly elevated secretory IgA, and a dysbiotic pattern. I had been suspicious of H. pylori for a specific reason. H. pylori may contribute to autoimmune gastritis through molecular mimicry with the gastric proton pump⁴, so in a patient who already had gastric autoimmunity, leaving an active infection in place felt like leaving a trigger switched on.

He started with a staged 60-day botanical protocol. It combined a biofilm-disrupting enzyme blend, monolaurin, sulforaphane glucosinolate, an antimicrobial herbal formula, and Saccharomyces boulardii. He added one agent at a time so we could attribute any reaction. When we repeated stool testing off treatment, H. pylori was still there.

At that point I laid out the options for him: a repeat botanical course or a choice of medication treatment protocols. He chose clarithromycin, amoxicillin, and omeprazole for 14 days. The follow-up stool testing 2 months later was negative. We then worked on restoring gut microbial balance and supporting the gut-immune response with targeted prebiotic, probiotic and gut lining support.

Immune Modulation as the Long Game

Once the nutrient, gut, and metabolic work was underway, I added low-dose naltrexone, titrated slowly over three months with the goal of immune modulation as a phase 1. We may have considered adding in an autoimmune paleo diet if needed. 

His TPO antibody sat above 900 for about two years. By the last full panel it was 418, and the thyroglobulin antibody had dropped from 523 to 118. He had gaps in his LDN and supplement adherence along the way but ultimately immune reactivity has reduced substantially and is represented in his labs, symptoms and health outcomes. 

The Hormone Foundations

Within 18 months, his glucose was stable and his gut work underway, his energy and recovery were still not where they should have been. A full androgen panel by mass spectrometry, along with zinc and DHEA-S, showed why.

Total testosterone looked acceptable. The usable fractions did not. A total of 433 ng/dL is the kind of number that gets called normal. But free testosterone of 75.1 pg/mL and bioavailable testosterone of 134.9 ng/dL both sat near the floor of their ranges. With SHBG at 25 nmol/L, binding was not the issue. The problem was supply.

The raw materials were thin. Zinc had slipped from 64 to 58 mcg/dL, now below range. Zinc is required for normal testosterone production, and restricting it in healthy men lowers serum testosterone while repletion in deficient men raises it⁵. In a man with autoimmune gastritis and wheat reactivity, falling zinc despite a good diet pointed back to absorption. DHEA-S, the adrenal precursor reservoir that peripheral tissues draw on to make active androgens, was low-normal at 100 mcg/dL.

Stress physiology was pulling in the other direction. His DUTCH test showed high total cortisol with low-normal free cortisol, low androgen metabolites, and a low DHEA-S. Chronic stress shifts the body’s resources toward cortisol production, and the androgen side of the system pays for it. Heavy travel, two drinks most nights, and a body still recovering from an immune crisis were all adding to that load.

And there was a sleep problem nobody had named yet. We ordered a sleep study that confirmed obstructive sleep apnea, which is strongly associated with low testosterone through fragmented sleep, intermittent hypoxia, and disrupted nocturnal hormone release⁶. He started CPAP, now uses it consistently, and credits it more than anything else for his energy.

DHEA: From Deficient to Restored

DHEA-S did not hold on its own. It drifted from 100 mcg/dL when first checked down to 54 mcg/dL, below the reference range. It turns out he had not been taking the recommended dose of DHEA, I had recommended. So, we added 25 mg of DHEA supplementation on top of the lifestyle work already in place, and on the most recent panel it had risen to 283 mcg/dL, comfortably within range.

His testosterone told a harder story. Despite the foundational work, his total testosterone later fell into the low 200s, and he independently coordinated with an outside men’s clinic for treatment. It’s important to consider that even when checking all of your foundational boxes, it may not improve everything and it’s ok to consider different tools for each patient, depending on their needs, goal and patient safety. 

Vitamin D: Eight Years to Make It Hold

His starting vitamin D of 10 ng/mL was not a one-time low. Across eight years of testing, it climbed when supplementation was pushed and then fell back, again and again.

Between 2018 and 2023 his levels ranged from 10 to 46 ng/mL and fell below the laboratory floor of 30 in four of seven measurements, even after he went gluten-free. This was a combination of inconsistent supplementation, dietary changes, falling in and out of treatment compliance and other variables. Removing wheat alone did not fix it. A fat-soluble vitamin that may not hold in a man with autoimmune gastritis, a persistent gastric infection, wheat reactivity, and elevated secretory IgA is a malabsorption story with more than one chapter. Vitamin D status also matters to the androgen picture: in one randomized trial, men with low vitamin D who were supplemented for a year saw a significant rise in total testosterone compared with placebo⁷.

The levels finally began to hold after his H. pylori was cleared, his gut work had time to take effect, and his sleep, alcohol, and adherence improved. Vitamin D reached 72 ng/mL in 2024 and 105 ng/mL in 2026. That last value overshot the laboratory upper limit of 100, so we cut his dose because it’s becoming clear that he is needing less and less supplementation as balance is being restored.

The Lifestyle Work That Carried the Load

It would be easy to read this patient case as a sequence of tests and prescription but the day-to-day work underneath it is what allowed those interventions to hold.

Diet. Strict wheat elimination, fewer processed foods, a protein-forward time-restricted pattern, and a glucometer to guide carbohydrates gave his gut, his glucose, and his liver a steadier environment.

Lifting. Progressive strength training built lean mass, improved insulin sensitivity, and supported androgen signaling. Resistance training produces acute increases in testosterone and favorable hormonal adaptations over time⁸. For a man coming off insulin, muscle was also his largest glucose sink.

Stress management. Heavy travel was not going to disappear, so we focused on what he could control: protected sleep windows on the road, short daily downregulation practices, and not stacking hard training on high-stress days. With his DUTCH showing high cortisol output and a falling DHEA-S, this was hormone treatment, not an afterthought.

Sleep and alcohol. CPAP changed his energy more than any supplement. His nightly drinking is still a work in progress and is now the main lever on his liver enzymes and the next main focus for him. 

Where He Stands Now

His LDL and ApoB improvements came with a higher statin dose added by his general practitioner, so I would credit the medication for this level of reduction. His ferritin fell to 15 in the past year, which fits the gastric picture, and responded to iron supplementation. His AST and ALT have drifted slightly up, so we are addressing his nightly drinking and rechecking. He later addedMounjaro, with his diabetes team for weight management. The work is not finished but he is stable, feeling great and has a better quality of life overall. 

What This Case Taught Me

Three conditions, hypothyroidism, a rare lymphadenitis, and a glucose crisis, looked like three separate problems. Screening through the lens that autoimmunity clusters turned them into one pattern and uncovered hashimoto’s and pernicious anemia, diagnoses nobody had been looking for. The Cyrex array added a source of daily immune stimulation that standard celiac testing would have missed. Working on the foundations, including nutrient repletion, a persistent gut infection, glycemic stability, sleep, stress, training, and hormones, gave his immune system a better environment to settle in. His antibody trends, inflammatory markers, vitamin D, and DHEA-S all moved in the right direction. No single intervention gets the credit.

If you manage patients with one autoimmune diagnosis, the practical takeaway is to ask what else the immune system might be doing and test for it before a second diagnosis surfaces on its own.

Learn the Clinical Reasoning Behind Cases Like This

If you want to learn the full investigative process behind this case, from screening for the second autoimmune diagnosis to sequencing testing to knowing when to stop chasing a number, the Adapt Functional Medicine Fellowship & Certification Program teaches that clinical reasoning across every system, with real world appointment shadowing on real patient cases. 

References

1. Cojocaru M, Cojocaru IM, Silosi I. Multiple autoimmune syndrome. Maedica (Bucur). 2010;5(2):132-134.
2. Cellini M, Santaguida MG, Virili C, et al. Hashimoto’s thyroiditis and autoimmune gastritis. Front Endocrinol (Lausanne). 2017;8:92.
3. Catassi C, Elli L, Bonaz B, et al. Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts’ Criteria. Nutrients. 2015;7(6):4966-4977.
4. Amedei A, Bergman MP, Appelmelk BJ, et al. Molecular mimicry between Helicobacter pylori antigens and H+,K+-adenosine triphosphatase in human gastric autoimmunity. J Exp Med. 2003;198(8):1147-1156.
5. Prasad AS, Mantzoros CS, Beck FW, Hess JW, Brewer GJ. Zinc status and serum testosterone levels of healthy adults. Nutrition. 1996;12(5):344-348.
6. Kim SD, Cho KS. Obstructive sleep apnea and testosterone deficiency. World J Mens Health. 2019;37(1):12-18.
7. Pilz S, Frisch S, Koertke H, et al. Effect of vitamin D supplementation on testosterone levels in men. Horm Metab Res. 2011;43(3):223-225.
8. Kraemer WJ, Ratamess NA. Hormonal responses and adaptations to resistance exercise and training. Sports Med. 2005;35(4):339-361.