18-03-2025
THIS IS AN ONLINE E LOG BOOK TO DISCUSS OUR PATIENT'S DE-IDENTIFIED HEALTH DATA SHARED AFTER TAKING HIS SIGNED INFORMED CONSENT. HERE WE DISCUSS OUR PATIENT'S PROBLEMS THROUGH SERIES OF INPUTS FROM AVAILABLE GLOBAL ONLINE COMMUNITY EXPERTS WITH AN AIM TO SOLVE THOSE PATIENT'S CLINICAL PROBLEMS WITH COLLECTIVE CURRENT BEST EVIDENCE BASED INPUTS.
DESCRIPTION
28y/M
k/c/o Hypothyroidism came for routine follow up
H/o easy fatigability + associated with body pains, not affecting daily life activities
H/o significant Hair loss (according to patient) diffuse, no patchy areas on scalp
H/o weight loss 3kgs in a month
H/o darkish discolouration + around the neck
no c/o constipation, abnormal weight gain, lethargy, palpitations
k/c/o hypothyroidism since his 12 years of age on medication Thyronorm 175mg
H/o constipation +
H/o haemorrhidectomy 2 years back
No other comorbidities
Trunkal obesity +
FAMILY HISTORY:
Father, (RMP by profession), died when the patient was of 4-5 yrs of age, due to unknown diabetic complication.
Mother, (housewife by occupation), died when the patient was an infant (he doesn't know any details about it)
Elder sister, died before he was born, details unknown about her mortality
Younger sister, died when the patient was about 1-2 yr old, details unknown about her mortality
ON PRESENTATION
pt is conscious, coherent,cooperative
Afebrile
Bp:110/70mmhg
PR: 70 bpm
RR: 16cpm
Spo2 :99% at room air
cvs: s1s2 heard, (loud S2, soft S1), no murmurs
Rs: BAE present, normal vesicular breath sounds, no added sounds
P/A: soft and non-tender
Cns : No focal neurological
deficit
No delayed reflexes
grbs : 108 mg/dl
[18-03-2025 19:32] PPM 1: 👆@PPM2 check out this patient's TFT inspite of being on 175 mcg thyroxine since 12 years !!
@PPM3 please remove the images of his eyes as they may serve as identifiers. Also pm @CR the
signed informed consent form for her to create the case report.
[18-03-2025 19.33] PPM 3: Ok sir.
[18-03-2025 19:34] PPM 1: @PPM3 tell us more about how he was diagnosed with hypothyroidism 12 years back and his hypothyroidism journey since last 12 years.
How frequently did he check his TFTs?
[18-03-2025 19:40] PPM 3: He was apparently shorter than his peers in school. So his father, being an RMP, took him to a hospital in Hyderabad and got some investigations done as a general checkup. Which incidentally led to him being diagnosed as hypothyroid.
[18-03-2025 19:41] PPM 3: He doesn't have the documents for previous checkups except for the recent one being 4months ago, by an endocrinologist, sir.
[18-03-2025 19:44] PPM 1: He might remember if his TFTs were controlled since his age of 16 and at
what doses were they controlled then?
[18-03-2025 19:46] PPM 3: Before this endocrinologist checkup, he was on T. Thyronorm 100mcg sir
[18-03-2025 19:46] PPM 1: And we repeated our TFT here after how many days of 175 mcg?
[18-03-2025 19.47] PPM 3: After 10/08/2024 sir
[18-03-2025 19:47] PPM 3: 7 months sir
[19-03-2025 07:20] PPM 1: 👆@PPM2 your endocrine inputs needed here
[19-03-2025 16.33] PPM 1: https://youtube.com/shorts/TCIxvI_3ctM?feature=shared
[19-03-2025 16:41] PPM 2: We need Free T4 and Free T3. How and when is the patient taking the
LTX?
[19-03-2025 16:41] PPM 2: Tbh I would check for Addisons in him.
[19-03-2025 16:43] PPM 2: When does he take his tablets and at what time?
[19-03-2025 16:49] PPM 1: 👆@PPM3
[19-03-2025 18.15] PPM 3: Till now, he was quite irregular with his medications sir. Sometimes he'd
take around 3-4am. Sometimes it's in the morning but he'd only wait for about 15-20mins and have his
breakfast, other times he'd forget to take his dose when travelling.
[19-03-2025 18:19] PPM 3: We asked him to wait for few more days for further evaluation, but he
apparently came unprepared and was willing to follow up with us later.
He's currently on his way home and was asked to review this Friday. But he told he couldn't this week,
but will come next Friday
[19-03-2025 19:55] PPM 1: Is he in this group?
[19-03-2025 19:56] PPM 3: Yes sir
[19-03-2025 20:01] PPM 1: Let's say he's the patient's immediate advocate just so that he
can remain deidentified in all conversations
[19-03-2025 20:01] PPM 3: Okay sir
[19-03-2025 21:09] PPM 2: This very likely answers it.
[19-03-2025 21:10] PPM 1: What could be the reason for his childhood onset
hypothyroidism?
[19-03-2025 21:19] PPM 2: The likeliest reason would be Autoimmunity. Either Hashimoto or as part of
Autoimmune Polyglandular Syndrome.
[19-03-2025 21:20] PPM 2: Which is why I'd offer screening for cortisol deficiency. Both very closely
mimic each other.
[11-07-2025 10.20] PPM 3: 
[11-07-2025 10:47] PPM 1: What was the need for TPO in a patient taking 175 mcg of thyroxine for 12 years? How much thyroxine is he on now? Also if you scan the qr code all identifiers will be visible so deidentification also necessitates removal of qr codes
[11-07-2025 10:57] PPM 3: 1. To confirm hashimoto's or other autoimmune conditions sir. And since his anti-tpo is true high, it'll also rule out any non compliance.
2. Currently he's on 200mcg sir
3. Okay sir
[11-07-2025 12:28] PPM 1: Please explain how TPO is related to compliance!
Also why do we need to confirm Hashimotos after 12 years! How would it change our management?
[11-07-2025 18.46] PPM 3: Excellent questions—let's clarify both the *compliance connection* and *why confirming Hashimoto's matters after 12 years* in this unique case of refractory hypothyroidism (TSH persistently >400).
---
### 1. *How Anti-TPO Relates to Compliance*
Anti-TPO antibodies *do not directly measure compliance, but they help **distinguish between true treatment resistance vs. non-adherence*:
- *If Anti-TPO is POSITIVE*:
- Strongly suggests *autoimmune destruction (Hashimoto's)* is driving high levothyroxine requirements.
- Points toward *malabsorption or comorbidities* (e.g., celiac disease, autoimmune gastritis) as the cause of uncontrolled TSH—*not poor compliance*.
- → Directs workup toward *GI testing, drug interactions, or antibody interference*.
- *If Anti-TPO is NEGATIVE*:
- Makes autoimmune thyroiditis less likely (though not impossible—10-15% of Hashimoto's is seronegative).
- Increases suspicion for:
- *Non-compliance* (patient not taking levothyroxine consistently).
- *Non-autoimmune causes* (e.g., iodine deficiency, pituitary dysfunction, assay interference).
- Rare conditions like *consumptive hypothyroidism* or TSH receptor mutations.
- → Focuses efforts on *adherence counseling, verifying medication quality, or repeating TSH with a different assay*.
#### Key Takeaway:
Anti-TPO status *guides where to look next* when treatment fails.
- ✅ *Positive TPO* → Investigate malabsorption/comorbidities.
- ❌ *Negative TPO* → Prioritize adherence verification and rule out assay errors.
---
### 2. *Why Confirm Hashimoto's After 12 Years?*
Even with a long history of hypothyroidism, confirming autoimmune etiology *changes management in 4 critical ways* for this patient:
#### 🔍 *a) Explains Refractory Hypothyroidism*
- Hashimoto's can cause *ongoing gland destruction*, increasing levothyroxine needs over time.
- Associated comorbidities (celiac disease, autoimmune gastritis) directly *impair T4 absorption*—requiring specific interventions:
- Example: Celiac disease (↑ in Hashimoto's patients) → Gluten-free diet improves T4 absorption.
- Example: Autoimmune gastritis → Low stomach acid → Needs liquid levothyroxine or thyroxine injections.
#### ⚠ *b) Identifies Risk for Blocking Antibodies*
- Rarely, Hashimoto's patients develop *blocking TSH receptor antibodies (TBII)*:
- Accelerate thyroid destruction → Higher T4 doses needed.
- Can interfere with TSH assays → Falsely elevated TSH readings.
- *Action: Order **TRAb (TSH receptor antibody) testing* to check for blocking activity.
#### 🤰 *c) Pregnancy Implications (If Applicable)*
- Hashimoto's (especially with ↑ anti-TPO) *increases risks*:
- Miscarriage, preterm birth, fetal neurodevelopmental issues.
- Postpartum thyroiditis (15% of women).
- *Action*:
- Target TSH *<2.5 mIU/L* in pregnancy (aggressive dose adjustments).
- Monitor TSH every 4 weeks during pregnancy.
#### 🧩 *d) Screens for Associated Autoimmune Conditions*
- Hashimoto's is linked to:
- *Type 1 diabetes* (check HbA1c).
- *Addison's disease* (AM cortisol/ACTH if fatigue/wt. loss).
- *Rheumatoid arthritis, lupus, etc.*
- *Action*: Proactively screen for symptoms/signs of these disorders.
---
### 🚨 Management Changes if Hashimoto's is Confirmed
| *Scenario* | *Actions* |
|----------------------------|-----------------------------------------------------------------------------|
| *Malabsorption* | Switch to *liquid levothyroxine* or *softgel capsules* (bypasses acid-dependent absorption). Space food/meds by 1 hour. |
| *Celiac disease* | Gluten-free diet + recheck TSH in 3 months; may need ↓ levothyroxine dose. |
| *Autoimmune gastritis* | Check B12/parietal cell antibodies; consider B12 injections. |
| *Blocking TRAb+* | Use *free T4 (not TSH)* to guide dosing; liaise with endocrinology. |
| *Pregnancy* | Immediately ↑ levothyroxine dose by 25–30%; target TSH <2.5 mIU/L. |
---
### ❗ Bottom Line
In *stable, controlled* hypothyroidism, confirming Hashimoto's after 12 years is unnecessary.
But in *refractory cases (TSH >400)*:
- Anti-TPO testing is *essential* to:
1. Rule out mimics (non-compliance, assay errors).
2. Unlock targeted workup for malabsorption/comorbidities.
3. Address pregnancy risks or blocking antibodies.
- *Changes management* from empiric dose adjustments to *precision interventions*.
Order anti-TPO now—alongside FT4, FT3, celiac serology, and TRAb—to act decisively.
[11-07-2025 19:29] PPM 1: Thanks. I'm assuming this is chatGPT. There are some areas of hallucinations such as mentioning TSH is above 400! Is it? I'm unable to see the TSH in the reports you have shared above now although I thought it was lower when you uploaded that too in the morning before you deleted them and uploaded again because of the presence of QR codes.
Also the statements made above by ChatGPT also kind of makes an insinuation that the thyroxine replacement dosage may depend on the degree of autoimmune activity? @PPM2
[11-07-2025 19:30] PPM 1: Please ask it to support it's statements above with perplexity styled searchable scientific articles
[11-07-202521.25] PPM 3: Outside TSH has been shown as >150 in documentation, and in another report it was ours it's given as 494. So I presumed the initial test could only detect till 150 or 100 hence anything greater is probably showing up as >(said limit)
[11-07-2025 21.26] PPM 3: This report he got it done outside sir recently
[11-07-2025 21:59] PPM 2: I personally think the Anti TPO antibodies have limited value in diagnosis and no value in dose titration or compliance.
[11-07-2025 22:02] PPM 2: Perhaps this will be a good reflection point for the trainees (including myself) I must admit at the beginning of one's training journey - the focus is on the nitty gritties and all sorts of stuff But as things progress - you tend to focus on patient outcomes.
Another subtle observation I made is that the best doctors are those who understand their economics well. Apart from the inherent value of the TPO in itself - was the journey to the lab for this test and the expenditure worth it? Unlikely.
[11-07-2025 22:05] PPM 2: Especially in a social Healthcare system such as in the UK
Just coming off of a CANC (combined Antenatal endocrine clinic) and one of the Obs consultant wanted the patient to come to the MDAU to get her BP checked 3 times in a 30 minute window. The patient was asking if she can do this herself at home and the consultant refused flatly, saying she wants to take "no risks"
Apart from being a bad decision clinically, this is an economically bad decision as well.
"What is medicine but politics!"
[12-07-2025 07:22] PPM 2: That consultant would be horrified to see and learn from our PaJR BP charts especially how many of our patients have actually been able to stop their anti hypertensive medications after weekly 24 hour home BP recording showed they didn't have any hypertension!
[13-07-2025 22.45] PPM 3: Is there anything we can do for this patient sir?
Other than continuing his thyroxine medication?
[14-07-2025 07.00] PPM 1: For that we need to know his clinical symptoms because till now we were mostly focused in treating his reports?
[18-07-2025 13:05] PPM 1: Please list his current symptoms
[05-08-2025 22:50] PPM 3: I apologize for the delay sir.
His symptoms and events since last admission/follow up, are as follows.
Headache, insidious onset, intermittent type, non-radiating type, in frontoparietal area, usually in the evening, no aggravating factors, headache usually lasting about 30 minutes to 1hr, resolved on its own or on taking rest. Resolved now on taking medications (prescribed in outside hospital)
H/o frequent rhinorrhea
Patient gives history of aversion to loud sounds (specifically honking) a/w intense anger response to honking since more than 10yrs (?misophonia).
No h/o giddiness, nausea, vomiting, blurring of vision, photophobia
H/o palpitations, intermittent type, during sleep, resolved after changing the medication to T. Thyronorm 125mcg po od (prescribed on ~15/07/25)
H/o dryness of b/l palms
[06-08-2025 08:13] PPM 1: From thyroxine 175 to 125 mcg?
And this is inspite of his recent thyroid function tests showing increased hypothyroidism?
[06-08-2025 08:13] PPM 1: 👆date?
[06-08-2025 09:35] PPM 3: Yes sir, that was what the patient advocate said
[06-08-2025 09:36] PPM 1: Who reduced it by 50mcg inspite of the tests indicating persistent hypothyroidism even on 175 mcg?
[06-08-2025 09:36] PPM 3: 7 th July 2025 sir
[06-08-2025 09:39] PPM 3: Apparently there was a doctor from Osmania, who in a medical camp near his place, prescribed such medication sir. The patient advocate told that he knows her (the said doctor) and that she runs a clinic in Hyderabad.
[12.32 pm, 24/01/2026] PPM 3: The patient got tested (on his own)
[6:58 pm, 24/01/2026] PPM 2: Quite possible there is Thyroid Hormone resistance or Absorption issues. How and when does he take the tablet?
[6:59 pm, 24/01/2026] PPM 2: Also which brand of Levothyroxine is he taking?
[7:18 pm, 24/01/2026] PPM 3: He takes it around 8-9am sir. That's apparently the first thing he does, and goes back to sleep for about an hour. After waking up (properly this time), he freshens up, eats his breakfast and gets on with his day
[3:45 am, 25/01/2026] PPM 2: @PaJR Health What are causes of Primary Hypothyroidism which get diagnosed at age 12 in men? Review the literature
[3:46 am, 25/01/2026] PaJR Health: *CAUSES OF PRIMARY HYPOTHYROIDISM IN CHILDHOOD AND ADOLESCENCE*
Based on a review of the medical literature, primary hypothyroidism diagnosed at age 12 in males can stem from several causes, with some being more common than others.
*COMMON CAUSES*
💡 *Hashimoto's Thyroiditis:* This autoimmune condition, also known as chronic lymphocytic thyroiditis, is the most frequent cause of acquired primary hypothyroidism in children and adolescents in developed nations. It involves the immune system attacking the thyroid gland.
*LESS COMMON / SPECIFIC CAUSES*
💡 *Iodine Deficiency:* Globally, insufficient iodine intake is a common cause of hypothyroidism, often leading to goiter.
💡 *Childhood Cancer Treatment:*
📍 *Radiation Therapy:* Exposure of the thyroid gland to radiation during treatment for pediatric cancers significantly increases the risk of primary hypothyroidism. The risk is influenced by the radiation dose and the patient's age at treatment.
📍 *Systemic Antineoplastic Therapy (Chemotherapy):* Certain chemotherapy drugs, such as high-dose interferon-alpha and tyrosine kinase inhibitors, have been linked to primary hypothyroidism in children during or after treatment.
📍 *Allogeneic Stem Cell Transplantation (allo-SCT):* Primary hypothyroidism is a known endocrine complication following allo-SCT in children. Higher thyroid-stimulating hormone (TSH) levels before transplantation can predict the onset of post-SCT hypothyroidism.
💡 *Thalassemia Major:* In patients with thalassemia major, iron overload from frequent blood transfusions can lead to primary hypothyroidism, typically appearing in the second decade of life. Early and intensive chelation therapy may reverse this.
💡 *Down Syndrome:* Children with Down syndrome have a higher prevalence of various thyroid dysfunctions, including acquired primary hypothyroidism, even when not autoimmune in origin.
💡 *Cystinosis:* This rare genetic disorder can also be a cause of primary hypothyroidism.
💡 *Pharmacological Interference:* Some medications can interfere with thyroid function and lead to hypothyroidism.
*ASSOCIATED CONDITIONS AND PRESENTATIONS*
💡 *Pituitary Hyperplasia:* Prolonged and untreated primary hypothyroidism in children can lead to pituitary gland enlargement, which might be mistaken for a tumor. This is a compensatory response to the underactive thyroid.
💡 *Van Wyk-Grumbach Syndrome (VWGS):* This rare syndrome occurs in cases of severe, long-standing juvenile hypothyroidism. It is characterized by delayed growth and bone maturation, but paradoxically, can present with peripheral precocious puberty and pituitary enlargement. In boys, testicular enlargement is a notable feature.
💡 *Hyperprolactinemia:* Elevated prolactin levels are frequently observed in children with subclinical and overt primary hypothyroidism.
💡 *Rhabdomyolysis:* In very rare instances, severe hypothyroidism, often due to Hashimoto's thyroiditis, can manifest as rhabdomyolysis in adolescents.
💡 *Macroorchidism:* Long-standing primary hypothyroidism can be an endocrine cause of enlarged testes in childhood and adolescence.
While some studies mention gender, the underlying causes of acquired hypothyroidism in childhood and adolescence are generally similar for both males and females, though specific risk factors may have varying impacts.
*LITERATURE REVIEW*
📍 Acquired Hypothyroidism in Children - [PMID: 37256446](https://pubmed.ncbi.nlm.nih.gov/37256446/)
📍 Primary hypothyroidism in childhood cancer survivors: Prevalence, risk factors, and long-term consequences - [PMID: 34643950](https://pubmed.ncbi.nlm.nih.gov/34643950/)
📍 Thyroid disorders in childhood and adolescence. Part 2: Hypothyroidism - [PMID: 33459001](https://pubmed.ncbi.nlm.nih.gov/33459001/)
📍 Evaluation and management of the child with hypothyroidism - [PMID: 30734891](https://pubmed.ncbi.nlm.nih.gov/30734891/)
📍 Pituitary hyperplasia in childhood primary hypothyroidism: a review - [PMID: 33404718](https://pubmed.ncbi.nlm.nih.gov/33404718/)
📍 Primary Hypothyroidism in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review - [PMID: 33810948](https://pubmed.ncbi.nlm.nih.gov/33810948/)
📍 Macroorchidism in childhood and adolescence: an update - [PMID: 24683950](https://pubmed.ncbi.nlm.nih.gov/24683950/)
📍 Growth and endocrine function in thalassemia major in childhood and adolescence - [PMID: 20203539](https://pubmed.ncbi.nlm.nih.gov/20203539/)
📍 Hypothalamic dysfunction after chemotherapy - [PMID: 14960022](https://pubmed.ncbi.nlm.nih.gov/14960022/)
📍 Down syndrome and nonautoimmune hypothyroidisms in neonates and infants - [PMID: 25592247](https://pubmed.ncbi.nlm.nih.gov/25592247/)
📍 L-T4 Therapy in the Presence of Pharmacological Interferents - [PMID: 33414765](https://pubmed.ncbi.nlm.nih.gov/33414765/)
📍 Hyperprolactinemia in Children with Subclinical Hypothyroidism - [PMID: 28529200](https://pubmed.ncbi.nlm.nih.gov/28529200/)
📍 Primary juvenile hypothyroidism concurrent with huge bilateral cystic ovaries: Case report and literature review - [PMID: 33339721](https://pubmed.ncbi.nlm.nih.gov/33339721/)
📍 Primary hypothyroidism with pituitary hyperplasia characterized by hypogonadotropic hypogonadism: a case report and review of the literature - [PMID: 33183016](https://pubmed.ncbi.nlm.nih.gov/33183016/)
📍 Primary hypothyroidism in cystinosis - [PMID: 874698](https://pubmed.ncbi.nlm.nih.gov/874698/)
📍 Thyroid dysfunction during treatment with systemic antineoplastic therapy for childhood cancer: A systematic review - [PMID: 36907363](https://pubmed.ncbi.nlm.nih.gov/36907363/)
📍 Long-term endocrine sequelae of childhood cancer - [PMID: 17630615](https://pubmed.ncbi.nlm.nih.gov/17630615/)
📍 Severe Acquired Primary Hypothyroidism in Children and its Influence on Growth: A Retrospective Analysis of 43 Cases - [PMID: 34607373](https://pubmed.ncbi.nlm.nih.gov/34607373/)
📍 Endocrine complications in patients with Thalassaemia Major - [PMID: 18084158](https://pubmed.ncbi.nlm.nih.gov/18084158/)
📍 Van Wyk Grumbach Syndrome and Ovarian Hyperstimulation in Juvenile Primary Hypothyroidism: Lessons From a 30-Case Cohort - [PMID: 37197410](https://pubmed.ncbi.nlm.nih.gov/37197410/)
📍 Rhabdomyolysis: A Rare Presentation of Hashimoto Thyroiditis in an Adolescent Boy and Review of the Literature - [PMID: 36780885](https://pubmed.ncbi.nlm.nih.gov/36780885/)
📍 Impact of allogeneic stem cell transplantation on thyroid function - [PMID: 36884196](https://pubmed.ncbi.nlm.nih.gov/36884196/)
[3:49 am, 25/01/2026] PPM 2: Thanks. Appears like this is autoimmune and the patient likely has Hashimoto's. He was on Levothyroxine 175ug and inspite of that his TSH was very high (~18 mIU). What are potential explanations for this?
[3:49 am, 25/01/2026] PaJR Health: It's concerning that your patient's TSH remains very high (around 18 mIU/L) despite being on a high dose of Levothyroxine (175 ug), especially with a likely diagnosis of Hashimoto's thyroiditis. This suggests that the Levothyroxine isn't being effectively utilized by the body. Here are potential explanations based on the literature:
*1. MALABSORPTION OF LEVOTHYROXINE*
💡 *Gastrointestinal Issues:* Levothyroxine absorption primarily occurs in the small intestine. Various gastrointestinal disorders can impair this absorption.
📍 *Lactose Intolerance:* This is a common issue in patients with Hashimoto's thyroiditis. Studies show that lactose restriction can significantly decrease TSH levels in these patients, suggesting that lactose in medication or diet can interfere with Levothyroxine absorption.
📍 *Other Malabsorptive Conditions:* Conditions affecting the gut can lead to poor absorption.
📍 *Bariatric Surgery:* While not directly applicable to a 12-year-old, Roux-en-Y gastric bypass surgery has been shown to delay Levothyroxine absorption, highlighting how changes in the gastrointestinal tract can impact medication efficacy.
💡 *Drug and Food Interactions:* Numerous substances can interfere with Levothyroxine absorption if taken concurrently.
📍 *Calcium Supplements:* Calcium carbonate, citrate, and acetate can significantly reduce Levothyroxine absorption.
📍 *Iron Supplements*
📍 *Antacids (e.g., aluminum hydroxide, magnesium hydroxide)*
📍 *Certain Medications:* Ciprofloxacin (an antibiotic) has been shown to decrease Levothyroxine absorption. Other medications, like amiodarone, can also affect thyroid function and hormone metabolism.
📍 *Food Intake:* Taking Levothyroxine with food, especially high-fiber foods, can reduce its absorption. It's generally recommended to take it on an empty stomach, 30-60 minutes before breakfast.
💡 *Levothyroxine Formulation:* Different formulations (tablet, liquid solution, soft gel capsule) can have varying absorption rates. Liquid or soft gel capsule formulations may be more rapidly absorbed and can overcome some interactions with foods, drugs, or malabsorptive conditions compared to tablets.
*2. PSEUDOMALABSORPTION (NON-ADHERENCE)*
💡 *Intentional Non-adherence:* This refers to situations where the patient is not consistently taking the medication as prescribed. While challenging to assess, it's a possibility to consider in cases of persistently high TSH despite seemingly adequate dosing. The Levothyroxine absorption test (LT4AT) can help distinguish true malabsorption from non-adherence.
*3. INCREASED LEVOTHYROXINE CLEARANCE OR METABOLISM*
💡 *Drug Interactions:* Some medications can increase the metabolism or clearance of Levothyroxine, leading to lower effective levels. For example, rifampin (an antibiotic) has been shown to increase T4 AUC, but other drugs can have the opposite effect.
💡 *High Expression of Efflux Transporters:* In rare cases of treatment-resistant Hashimoto's thyroiditis, high expression and accelerated efflux transporter activity (like ABCG2/BCRP) in the small intestine might contribute to the ineffectiveness of orally administered intact tablets. Crushing tablets has been shown to improve TSH levels in such cases.
*4. OTHER FACTORS*
💡 *Reference Ranges:* While less likely given a TSH of 18 mIU/L, it's worth noting that childhood TSH reference ranges can vary, and factors like age, sex, and ethnicity can influence thyroid function test results. However, a TSH of 18 mIU/L is clearly elevated beyond normal ranges for a 12-year-old.
💡 *Concurrent Illnesses:* Acute or chronic illnesses can sometimes affect thyroid hormone levels, though typically this would be considered in the context of "sick euthyroid syndrome," which usually involves normal TSH or slightly altered TSH with low T3/T4, not persistently high TSH on replacement therapy.
*RECOMMENDATIONS FOR INVESTIGATION*
Given the patient's high TSH despite a high Levothyroxine dose, it would be prudent to investigate:
* *Medication Adherence:* Discuss medication-taking habits with the patient and guardian.
* *Timing of Medication:* Ensure Levothyroxine is taken consistently on an empty stomach, separated from food, drinks (other than water), and other medications by at least 30-60 minutes.
* *Concomitant Medications/Supplements:* Review all other medications, vitamins, and supplements the patient is taking for potential interactions.
* *Dietary Factors:* Inquire about dietary habits, especially lactose intake.
* *Gastrointestinal Evaluation:* Consider evaluating for malabsorptive conditions if other factors are ruled out.
* *Levothyroxine Absorption Test (LT4AT):* This test can be valuable in differentiating between malabsorption and non-adherence.
*LITERATURE REVIEW*
📍 Gastrointestinal Malabsorption of Thyroxine - [PMID: 30476027](https://pubmed.ncbi.nlm.nih.gov/30476027/)
📍 A Case of Hashimoto's Thyroiditis with Multiple Drug Resistance and High Expression of Efflux Transporters - [PMID: 31614366](https://pubmed.ncbi.nlm.nih.gov/31614366/)
📍 Precision Medicine in Autoimmune Thyroiditis and Hypothyroidism - [PMID: 34867359](https://pubmed.ncbi.nlm.nih.gov/34867359/)
📍 Thyroid function, autoimmunity, thyroid volume, and metabolic profile in people with Hashimoto thyroiditis - [PMID: 39741265](https://pubmed.ncbi.nlm.nih.gov/39741265/)
📍 Subclinical hypothyroidism or isolated high TSH in hospitalized patients with chronic heart-failure and chronic renal-failure - [PMID: 34040018](https://pubmed.ncbi.nlm.nih.gov/34040018/)
📍 Newborn screening for congenital hypothyroidism - [PMID: 23154158](https://pubmed.ncbi.nlm.nih.gov/23154158/)
📍 A Review of the Pharmacokinetics of Levothyroxine for the Treatment of Hypothyroidism - [PMID: 30349610](https://pubmed.ncbi.nlm.nih.gov/30349610/)
📍 Subclinical hypothyroidism in childhood and adolescense - [PMID: 25153584](https://pubmed.ncbi.nlm.nih.gov/25153584/)
📍 Detection and treatment of congenital hypothyroidism - [PMID: 22009163](https://pubmed.ncbi.nlm.nih.gov/22009163/)
📍 Childhood Thyroid Function Reference Ranges and Determinants: A Literature Overview and a Prospective Cohort Study - [PMID: 28942709](https://pubmed.ncbi.nlm.nih.gov/28942709/)
📍 The Stability of TSH, and Thyroid Hormones, in Patients Treated With Tablet, or Liquid Levo-Thyroxine - [PMID: 33790863](https://pubmed.ncbi.nlm.nih.gov/33790863/)
📍 Hashimoto's Thyroiditis and Female Infertility: A Clinical and Statistical Investigation of Endocrine and Ovarian Markers - [PMID: 40649144](https://pubmed.ncbi.nlm.nih.gov/40649144/)
📍 Assessment of glucose and lipid metabolism in patients with polycystic ovary syndrome with and without Hashimoto's thyroiditis - [PMID: 36930082](https://pubmed.ncbi.nlm.nih.gov/36930082/)
📍 Intestinal absorption and buccal absorption of liquid levothyroxine - [PMID: 28271396](https://pubmed.ncbi.nlm.nih.gov/28271396/)
📍 A Comparative Study on Insulin Secretion, Insulin Resistance and Thyroid Function in Patients with Polycystic Ovary Syndrome with and without Hashimoto's Thyroiditis - [PMID: 33953581](https://pubmed.ncbi.nlm.nih.gov/33953581/)
📍 Update on the management of congenital hypothyroidism - [PMID: 18174723](https://pubmed.ncbi.nlm.nih.gov/18174723/)
📍 The various effects of amiodarone on thyroid function - [PMID: 11396710](https://pubmed.ncbi.nlm.nih.gov/11396710/)
📍 Absorption of levothyroxine when coadministered with various calcium formulations - [PMID: 21595516](https://pubmed.ncbi.nlm.nih.gov/21595516/)
📍 The Levothyroxine Absorption Test: A Four-Year Experience (2015-2018) at The Mayo Clinic - [PMID: 31680654](https://pubmed.ncbi.nlm.nih.gov/31680654/)
📍 High circulating levels of sICAM-1 and sVCAM-1 in the patients with Hashimoto's thyroiditis - [PMID: 27366829](https://pubmed.ncbi.nlm.nih.gov/27366829/)
📍 Are We Missing Hypothyroidism among Children with Sickle Cell Anaemia? - [PMID: 38784480](https://pubmed.ncbi.nlm.nih.gov/38784480/)
📍 Levothyroxine absorption in morbidly obese patients before and after Roux-En-Y gastric bypass (RYGB) surgery - [PMID: 21633823](https://pubmed.ncbi.nlm.nih.gov/21633823/)
📍 L-T4 Therapy in the Presence of Pharmacological Interferents - [PMID: 33414765](https://pubmed.ncbi.nlm.nih.gov/33414765/)
📍 Pharmacokinetics of coadministration of levothyroxine sodium and alendronate sodium new effervescent formulation - [PMID: 28204953](https://pubmed.ncbi.nlm.nih.gov/28204953/)
📍 Decrease in TSH levels after lactose restriction in Hashimoto's thyroiditis patients with lactose intolerance - [PMID: 24078411](https://pubmed.ncbi.nlm.nih.gov/24078411/)
📍 Selenium and its relationship with selenoprotein P and glutathione peroxidase in children and adolescents with Hashimoto's thyroiditis and hypothyroidism - [PMID: 26854239](https://pubmed.ncbi.nlm.nih.gov/26854239/)
📍 Ciprofloxacin and rifampin have opposite effects on levothyroxine absorption - [PMID: 23647409](https://pubmed.ncbi.nlm.nih.gov/23647409/)
📍 Low Value of Thyroid Testing in the Pediatric Inpatient Setting - [PMID: 30559318](https://pubmed.ncbi.nlm.nih.gov/30559318/)
📍 Evaluating the role of resistive index in pediatric Hashimoto's thyroiditis diagnosis and the impact of vitamin D treatment on resistive index - [PMID: 41272592](https://pubmed.ncbi.nlm.nih.gov/41272592/)
[3:49 am, 25/01/2026] PPM 2: Thanks. Did the patient ever receive an US scan of his Neck/Thyroid?
[3:54 am, 25/01/2026] PPM 2: @PPM3 some of his clinical symptoms and signs do raise the possibility of APS 2. 3 questions you could consider?
1. Does he take his LTX daily without fail?
2. Does he have any symptoms of malabsorption
3. Can you help describe the weight loss further? Voluntary or involuntary? Salt craving? What about the blackish discoloration? Insulin resistance Acanthosis or pigmentation in non sun exposed areas?
Would be very helpful. Thanks again.
[3:55 am, 25/01/2026] PPM 2: Please present data from the Levothyroxine absorption test study done at Mayo clinic.
[3:55 am, 25/01/2026] PaJR Health: *LEVOTHYROXINE ABSORPTION TEST DATA FROM MAYO CLINIC*
A study conducted at the Mayo Clinic, reviewing a four-year experience (2015-2018) with the Levothyroxine (LT4) absorption test, provides valuable insights into its utility for patients with refractory hypothyroidism.
*STUDY OBJECTIVES*
💡 To determine the test's effectiveness in distinguishing between LT4 malabsorption and pseudomalabsorption (intentional non-adherence).
💡 To assess the impact of test results on physician management decisions.
💡 To report on clinical outcomes during follow-up.
*METHODOLOGY*
💡 *Participants:* 16 patients diagnosed with refractory hypothyroidism who underwent the LT4 absorption test.
💡 *Test Procedure:* A six-hour test where patients received a weight-based dose of LT4, followed by serial measurements of total thyroxine (TT4) and thyroid-stimulating hormone (TSH).
💡 *Absorption Calculation:* Percentage absorption was calculated using a specific formula, with normal absorption defined as ≥60%.
*KEY FINDINGS*
💡 *Absorption Results:*
📍 Percentage absorption was calculated for 13 of the 16 patients.
📍 *Impaired Absorption:* One patient showed impaired absorption (0% absorbed), and this patient had known causes of malabsorption.
📍 *Normal Absorption:* The remaining 12 patients demonstrated normal absorption (60-158% absorption) by hour 4 of the test, accompanied by upward trends in TT4.
💡 *Clinical Impact:*
📍 Clinical follow-up ranged from 1 to 32 months (median 6.5 months) for 11 patients with available data.
📍 *Improved Outcomes:* Six patients achieved normal or suppressed TSH levels at their most recent follow-up.
📍 *Persistent Elevations:* Four patients showed improved but still elevated TSH levels.
📍 *Intravenous LT4:* The patient with confirmed malabsorption improved with intravenous LT4 therapy.
*CONCLUSION*
The study concluded that the Levothyroxine absorption test can provide valuable information to differentiate between true malabsorption and pseudomalabsorption (non-adherence). The findings support using calculated percentage absorption alongside TT4 trends over at least a four-hour period to determine absorption efficacy.
*LITERATURE REVIEW*
📍 The Levothyroxine Absorption Test: A Four-Year Experience (2015-2018) at The Mayo Clinic - [PMID: 31680654](https://pubmed.ncbi.nlm.nih.gov/31680654/)
[3:59 am, 25/01/2026] PPM 2: Thanks. What was the formula used to calculate the absorption? If the study does not have it, what is the general formula used?
[3:59 am, 25/01/2026] PPM 2: Thanks. What was the formula used to calculate the absorption? If the study does not have it, what is the general formula used?
[4:00 am, 25/01/2026] PaJR Health: The abstract for the Mayo Clinic study (PMID: 31680654) states that "Percentage absorption is calculated using the following formula, with normal absorption being >/=60%: [Formula: see text]". However, the specific formula itself was not detailed in the abstract.
In general, when assessing levothyroxine absorption in a clinical setting through a single-dose absorption test, the principle involves measuring the change in serum total thyroxine (TT4) levels over time after administering a large oral dose of levothyroxine.
While there isn't one universally standardized "formula" that provides a precise percentage in all clinical contexts without specific reference values (such as an intravenous comparison), the assessment typically involves:
* *Baseline Measurement:* Obtaining a serum TT4 level before administering the oral levothyroxine dose.
* *Serial Measurements:* Taking subsequent serum TT4 measurements at timed intervals (e.g., 2, 4, 6 hours) after the dose.
A significant rise in serum TT4 from the baseline value indicates adequate absorption. Different clinical protocols may define "normal" absorption based on:
* *Absolute Increase:* A specific increase in TT4 concentration (e.g., an increase of >2.0-3.0 mcg/dL).
* *Percentage Increase:* A calculated percentage rise in TT4 from baseline.
* *Area Under the Curve (AUC):* More complex pharmacokinetic analyses might calculate the area under the concentration-time curve for TT4 and compare it to known pharmacokinetic data or a theoretical maximum absorption for the given dose. The Mayo Clinic study's mention of "percentage absorption" and a range (60-158%) suggests a quantitative calculation, possibly based on an AUC approach or a comparison to an expected absorption value.
[4:01 am, 25/01/2026] PPM 2: This was the formula used
[4:01 am, 25/01/2026] PaJR Health: Thank you for providing the image of the formula!
The formula used to calculate the percentage of Levothyroxine (LT4) absorbed, as presented in the Mayo Clinic study, is:
*% Absorbed = [[Increment TT4 (mcg/dL) × 10 (dL/L)] / total administered LT4 (mcg)] × Vd(L) × 100*
Where:
* *Increment TT4 (mcg/dL):* This refers to the increase in total thyroxine (TT4) concentration in micrograms per deciliter.
* *10 (dL/L):* This is a conversion factor from deciliters to liters.
* *total administered LT4 (mcg):* This is the total dose of Levothyroxine administered in micrograms.
* *Vd(L):* This represents the volume of distribution in liters.
* *100:* This factor converts the result into a percentage.
[4:03 am, 25/01/2026] PPM 2: Thanks for teaching us. Please save all of these conversations to the patient's record.
[4:03 am, 25/01/2026] PaJR Health: The entire conversation has been saved to the patient's record.
[6:37 am, 25/01/2026] PPM 3: Yes sir
[6.45 am, 25/01/2026] PPM 3: 1. Patient insists that he does sir.
2. Patient apparently has no problems with his diet or bowels sir. He denies any frequent history of diarrhea, flatulence, bloating (sometimes occasional, but nothing significant), abdominal pain, weight loss.
3. He doesn't have any weight loss history, infact he does have weight gain history sir. No specific salt craving. He does seem to have acanthosis/pigmentation on the nape of his neck
[6:57 am, 25/01/2026] PaJR Health: *MEDICAL REPORT ANALYSIS*
*REPORT DATE:* 18/03/2025
*PATIENT AGE:* 28 years old, Male
*USG NECK FINDINGS*
*THYROID*
💡 *Right Lobe:* 9 x 12 x 21 mm
💡 *Isthmus:* 1 mm
💡 *Left Lobe:* 13 x 8 x 18 mm
💡 *Echotexture:* Altered echotexture noted in both lobes.
💡 *Lesion:*
📍 An 11 x 10 mm well-defined solid lesion is noted in the right lobe of the thyroid.
📍 The lesion is wider than tall.
📍 Vascularity is noted within the lesion.
📍 *TIRADS Classification:* TIRADS III lesion.
*LYMPHADENOPATHY*
💡 Few prominent lymph nodes are noted on the right side at levels IB and II.
💡 The largest lymph node measures 5 mm at level II.
💡 Prominent lymph nodes are also noted on the left side at levels IB and II.
💡 The largest lymph node measures 5 mm at level II.
*OTHER FINDINGS*
💡 Bilateral jugular and carotid vessels: Normal.
💡 Bilateral parotid and submandibular glands: Normal.
*IMPRESSION*
💡 TIRADS III lesion in the right lobe of the thyroid.
💡 Altered echotexture of the thyroid.
💡 Thyroiditis.
[6:58 am, 25/01/2026] PPM 2: Apply BTA U classification and grade this
[6:58 am, 25/01/2026] PaJR Health: *BTA U CLASSIFICATION AND GRADE*
Based on the provided USG Neck Findings, the thyroid lesion can be classified and graded as follows:
*BTA U CLASSIFICATION*
💡 *U3 - Equivocal / Indeterminate*
*RATIONALE FOR CLASSIFICATION*
The classification of U3 is assigned due to the presence of features that are mildly suspicious, aligning with the TIRADS III impression provided in the report.
📍 *Solid Lesion:* The report describes an "11 x 10 mm well-defined solid lesion" in the right lobe. Solid nodules can be benign or malignant, but their solid nature contributes to a higher suspicion category than purely cystic lesions.
📍 *Vascularity:* "Vascularity is noted within the lesion." While not specified as prominent central vascularity (a highly suspicious feature), the presence of internal vascularity is a feature that can be seen in U3 nodules.
📍 *Wider than Tall:* The lesion being "wider than tall" is generally considered a reassuring feature, often associated with benign nodules. This feature prevents it from being classified into a higher suspicion category (U4 or U5) which typically includes nodules that are "taller than wide."
📍 *TIRADS III:* The explicit mention of "TIRADS III lesion" directly correlates with a mildly suspicious nodule, which is consistent with a BTA U3 classification.
*OVERALL IMPRESSION*
💡 *Grade:* Low suspicion for malignancy.
*ADDITIONAL FINDINGS*
💡 *Altered Echotexture:* The "altered echotexture noted in both lobes" is often indicative of underlying thyroiditis (inflammation of the thyroid gland), such as Hashimoto's thyroiditis.
💡 *Lymph Nodes:* The prominent lymph nodes (largest 5 mm) at levels IB and II bilaterally are generally within normal limits for size and morphology, and do not, in isolation, suggest metastatic disease.
[6:59 am, 25/01/2026] PPM 2: Very helpful thank you!
[7:00 am, 25/01/2026] PPM 2: @PPM3 It seems this thyroid nodule should have been FNAC'd
[7:47 am, 25/01/2026] PPM 3: Will ask the patient to get it done sir
[7:33 pm, 25/01/2026] PPM 1: @PPM4 just to explicitly signpost certain roles and elements of the PaJR workflow contextually here with relevance to what was discussed in the welcome group yesterday:
@PPM3 is the local doctor here and the patient's second advocate and he has actually also created this group himself in March 2025.
While during @PPM5 's time this may have been more common for the local doctors to get it done, currently it's rare.
However as demonstrated above and hopefully archived by now for those who joined late, what has really changed for the better is the quality of global feedback the local doctor can now receive , which may not have been the same during @PPM5's time because now other than human agentic global doctor inputs we have a lot of quality LLM inputs, provided local doctors are able to process the TLDR threats, the current volume of information poses.
[7:50 pm, 25/01/2026] PPM 2: Dose entha teeskuntunaru mee patient?
[8:07 pm, 25/01/2026] PA: Yes
[8:45 pm, 25/01/2026] PPM 2: Dose is 125 mcg you mean?
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