Why TSH is so high

• Up to 50% of patients on long-term levothyroxine have TSH above range because of poor compliance (Tietz Textbook of Laboratory Medicine, 7th ed, Treatment of Hypothyroidism).
• Tietz also lists poor compliance as a cause of raised TSH with normal or borderline fT4.
• A borderline low T4 with a very high TSH is typical of this pattern. Some patients take the tablet in the days before the blood test, which lifts fT4 partly. TSH responds more slowly, so it stays very high.

• Erratic dosing, such as extra tablets just before the test.
• Residual thyroid function or recovering thyroiditis.
• Recovery from non-thyroidal illness.
• A drug or biotin effect on the assay.

• Calcium, iron, antacids, sucralfate, and bile acid sequestrants (Goodman & Gilman's, levothyroxine dosage requirements table).
• PPIs and taking the tablet with food or coffee (Katzung's, Case Study Answer).
• Other causes: celiac disease, atrophic gastritis, H. pylori, and bariatric surgery or short gut.
• Increased metabolism from rifampin, sertraline, or anticonvulsants (Berek & Novak's, Treatment).
• Other causes of higher requirement: weight gain, pregnancy, tyrosine kinase inhibitors, and loss of residual thyroid function in Hashimoto's.

• Biotin supplements can falsely alter immunoassays.
• Heterophile antibodies and macro-TSH can cause a falsely high TSH.
• Tietz lists heterophilic antibody interference among the causes of raised TSH with normal fT4.
• Repeat the test on a different platform, with PEG precipitation for macro-TSH if needed.
• Stop biotin for at least 48 to 72 hours before retesting.

Suggested approach

1. Ask directly about adherence, the timing of doses relative to food, and any new supplements or drugs.
2. Look for symptoms and signs of significant hypothyroidism. Check lipids, CK, and sodium. Urgent assessment is needed only if there are features of myxedema, such as hypothermia, bradycardia, or altered mentation.
3. Restore a consistent daily dose. About 1.6 mcg/kg/day is a typical full replacement dose, with an age and cardiac adjustment. Avoid a big jump if the patient has been taking tablets intermittently, because they may overshoot once they take it reliably.
4. Recheck TSH and fT4 after 6 to 8 weeks of consistent dosing. If adherence is the problem, a once-weekly dose is an option.
5. Screen for celiac disease and gastric causes if TSH stays high despite confirmed adherence and a proper dose.

• Check observations: temperature, HR, BP, RR, SpO2, glucose, GCS.
• Look for hypothermia, bradycardia, hypotension, hypoventilation, hyponatraemia, confusion, effusions, or ileus.
• If the patient is well, with only a borderline low fT4 and no features of decompensation, this is severe uncomplicated hypothyroidism. It does not need IV treatment and can be managed with oral levothyroxine.
• If there are features of myxedema coma, they will advise HDU/ICU, IV levothyroxine, and IV hydrocortisone. A typical regimen is hydrocortisone 100 mg IV every 8 hours until adrenal insufficiency is excluded, and local protocols vary. They will also look for a precipitant such as sepsis, drugs, or cold exposure.

• Repeat TSH, fT4, and fT3.
• Morning cortisol, or a random cortisol if the patient is unwell. Autoimmune adrenal insufficiency can coexist, and thyroid hormone can precipitate an adrenal crisis.
• U&E (especially sodium), glucose, FBC, CK, lipids, and LFTs.
• ECG, plus a CXR or echo if there are signs of effusion or heart failure.
• TPO antibodies if not already known. Also tissue transglutaminase IgA (coeliac) and B12.
• A drug history for calcium, iron, PPIs, antacids, biotin, amiodarone, lithium, and TKIs.
• If adherence is genuinely good and TSH is still above 100, ask the lab about biotin, heterophile antibody, or macro-TSH interference.

• Restart oral levothyroxine as an inpatient, given on an empty stomach 30 to 60 minutes before food and away from calcium or iron. Supervised doses also give a real picture of adherence.
• Dose: the previous 75 mcg is a reasonable restart for a patient with known requirements. They may go up to a full replacement dose of about 1.6 mcg/kg if the patient is young with no cardiac disease.
• If the patient is elderly or has ischaemic heart disease or AF, they will start lower (25 to 50 mcg) and titrate.
• Do not chase the TSH with early dose escalation. TSH lags fT4 by about 6 weeks.
• If there is a cortisol concern, they will cover with steroids before or alongside levothyroxine.

• If stable, discharge is usually fine with an outpatient plan. They do not need a long admission.
• Address why doses were missed: education, a pill organiser or alarm, and one fixed daily routine. If adherence stays poor, they may suggest a once-weekly dose (about 7 times the daily dose, with the endocrine team agreeing the dose).
• Repeat TSH and fT4 at 6 to 8 weeks, then titrate in 12.5 to 25 mcg steps. Dose changes should not rest on a single low TSH.
• Communicate the plan to the GP, including the fact that the earlier dose reduction was probably based on unreliable intake.

• How the patient looks (observations, mental state)
• The actual fT4 value
• Whether the patient is on other medications
• Whether they are pregnant, elderly, or have cardiac disease
• Any known adrenal or other autoimmune disease

What hypothyroidism does to the blood

• It typically causes a mild normocytic or slightly macrocytic anaemia. This is due to low erythropoietin and possibly a hypocellular marrow (Tietz Textbook of Laboratory Medicine, 7th ed, Signs; Rosen's Emergency Medicine, Clinical Features).
• It can cause acquired von Willebrand syndrome and platelet function problems. These produce bleeding with a normal or near-normal count (Tietz, reference on acquired von Willebrand syndrome associated with hypothyroidism).
• I found nothing in the library describing true thrombocytopenia as a direct effect. A PubMed search for recent systematic reviews on hypothyroidism and thrombocytopenia returned nothing relevant. Rare case reports exist, but I can't cite them.

Likely causes in this patient

• Immune thrombocytopenia (ITP) clusters with autoimmune thyroid disease, because polyautoimmunity is common. Harrison's lists autoimmune thrombocytopenia alongside autoimmune hypothyroidism.
• Also consider SLE, antiphospholipid syndrome, and Evans syndrome (ITP with autoimmune haemolysis).

• Pernicious anaemia often coexists with Hashimoto's. It causes macrocytosis, and in severe cases pancytopenia.
• Atrophic gastritis and coeliac disease would also fit the poor levothyroxine control.
• Look for a raised MCV, hypersegmented neutrophils, a low reticulocyte count, and a raised LDH and bilirubin.

• Alcohol or chronic liver disease can lower platelets through marrow suppression or hypersplenism.
• Alcohol or mental health problems may also explain the missed doses.

• Heparin (consider HIT if the patient is an inpatient on heparin, and check the timing)
• Antibiotics (for example linezolid or trimethoprim-sulfamethoxazole)
• Valproate, carbamazepine, and PPIs
• Lithium or amiodarone, which are thyroid-relevant
• Check every new drug started in the last 1 to 2 weeks.

• Look for schistocytes on the film, haemolysis, renal impairment, fever, or neurological change.
• Hypothyroid confusion can mimic this, so do not dismiss it.

Work-up

• FBC with film, reticulocytes, and MCV. Check whether other lines are low.
• B12, folate, ferritin, LFTs, LDH, bilirubin, haptoglobin, DAT, and urea and creatinine.
• PT, APTT, and fibrinogen.
• HIV, hepatitis B, and hepatitis C serology.
• ANA, dsDNA, and antiphospholipid antibodies.
• Tissue transglutaminase IgA, intrinsic factor and parietal cell antibodies, and H. pylori testing.
• Abdominal ultrasound for spleen size and liver.
• If there is mucocutaneous bleeding with a near-normal count, ask about von Willebrand factor levels. Acquired vWS from hypothyroidism improves with thyroid replacement.

Urgency

• Treat as urgent and involve haematology if platelets are below 20, there is active bleeding, or other cell lines are also low.
• Check platelets before any procedure, and avoid IM injections if the count is low.
• Tell the endocrine SpR when you call. A coexisting autoimmune process raises the chance of adrenal involvement, so cortisol matters even more before starting levothyroxine.