Thyroid

Q: What role does thyroid hormone play?

Thyroid hormone plays critical role in regulation/function of every organ system

Q: What is the correct sequence of the endocrine axis?

Hypothalamus → Pituitary → Thyroid → Tissue

Q: What is true about endocrine system dysfunction?

ENDOCRINE SYSTEM DYSFXN DOES NOT NECESSARILY FOLLOW A PREDICTABLE DECLINE

Q: What is true about thyroid disorders worldwide?

THYROID DISORDERS ARE MOST COMMON ENDOCRINE DISORDERS WORLDWIDE

Q: What is the prevalence of overt hypothyroidism?

1.7% overt

Q: What is the prevalence of hypothyroidism in females age > 65?

7.5% (♀)

Q: What is the prevalence of hypothyroidism in males age > 65?

2.5% (♂)

Q: What is the prevalence of subclinical hypothyroidism?

13.7% subclinical

Q: What is the gold standard diagnostic finding for hypothyroidism?

GOLD STANDARD DX: ↑ TSH w/ OR w/o FT4

Q: What does the thyroid secrete daily?

THYROID secretes T4 (~100 mcg daily) and T3 (~33 mcg daily)

Q: What is true about T4 activity?

T4 is INACTIVE / PRO-HORMONE – No T4 receptors in body

Q: What percentage of circulating thyroid hormone is T4 and what is its half-life?

T4 = 90%  T1/2 = 6–8 days

Q: What percentage of circulating thyroid hormone is T3 and what is its potency and half-life?

T3 = 10%  (4× more potent than T4)  T1/2 = 12–18 hrs

Q: Into what forms is T4 converted?

T4 converted to T3, rT3, [T3S, T3AC – Inactive]

Q: What percentage of T4 is bound to plasma proteins?

T4 bound (99%) to plasma proteins

Q: What is the order of decreasing affinity for T4 binding?

(↓ affinity – Thyroid-Binding Globulin > Transthyretin > Albumin)

Q: How does T3 binding affinity compare to T4?

T3 binds with 10–20× less affinity

Q: Where is most T3 produced and by what process?

Most T3 (80%) converted from T4 (deiodination) in extraglandular tissues (i.e., liver & kidneys)

Q: What is known about T1 & T2 secretion?

T1 & T2 secretion – limited and poorly defined function

Q: What is the major component secreted by the thyroid?

T4–Thyroxine → Major component secreted by thyroid

Q: What percentage of circulating hormone is T4?

98.5% of circulating hormone is T4

Q: How potent is T4?

Less potent hormone

Q: What is the minor component secreted by the thyroid?

T3–Triiodothyronine → Minor component secreted by thyroid

Q: What percentage of circulating hormone is T3?

1.5% of circulating hormone is T3

Q: How much T3 is converted from T4 and how much is secreted from the thyroid?

Majority of T3 converted from T4 (80%)

Q: How potent is T3 and what major function does it regulate?

More potent hormone – T3 regulates gene expression (a major function)

Q: What labs are used to evaluate safety and efficacy?

Evaluate along w/ TSH to evaluate safety and efficacy

Q: What forms of T3 or T4 can be measured?

Free and total T3 or T4

Q: What does total hormone represent?

Total = free + bound

Q: What is the title of the metabolic pathways shown?

Pathways of Thyroid Hormone Metabolism

Q: What note is made about expelled iodine?

• EXPELLED IODINE IS RE-USED

Q: What metabolic process produces DIT?

Ether bond cleavage (DIT)

Q: What metabolic process produces TA4?

Oxidative deamination (TA4)

Q: What metabolic process produces T4G?

Glucuronidation (T4G)

Q: What metabolic process produces T4S?

Sulfation (T4S)

Q: What metabolic process produces T3 and rT3?

Deiodination (T3 and rT3)

Q: Which deiodinases convert T4 → T3?

D1 & D2 converts T4 → T3

Q: How much stronger is D2 compared to D1?

D2 = 1000 x stronger than D1

Q: What does L-Thyroxine Rx rely on?

L-Thyroxine Rx relies on peripheral conversion of T4 → T3 (by D1 & D2)

Q: What percentage of peripheral T3 comes from D2 metabolism?

80% peripheral T3 comes from D2 metab

Q: What is the function of D3?

D3 → Clearance of both T4 & T3

Q: What does D3 convert T3 and T4 into?

T3 → T2 & T4 → rT3 (inactive)

Q: In what conditions is D3 increased?

↑↑ D3 in Hypoxia, Vascular Tumors, fibroblastic tumors, GI stromal tumors…

Q: What does decreased T3 concentrations indicate?

↓ T3 concs → Non-Thyroidal Illness

Q: What hair and eyebrow findings occur in hypothyroidism?

Dry, coarse hair

Q: What facial and thyroid findings occur in hypothyroidism?

Puffy face

Q: What cardiac and joint findings occur in hypothyroidism?

Slow heartbeat

Q: What temperature, mood, and skin findings occur in hypothyroidism?

Cold intolerance

Q: What energy and cognitive findings occur in hypothyroidism?

Fatigue

Q: What menstrual and reproductive findings occur in hypothyroidism?

Heavy menstrual periods

Q: What muscle, weight, bowel, and nail findings occur in hypothyroidism?

Muscle aches

Q: What hair and eye findings occur in hyperthyroidism?

Hair loss

Q: What sweating, thyroid, and cardiac findings occur in hyperthyroidism?

Sweating

Q: What sleep, temperature, and reproductive findings occur in hyperthyroidism?

Difficulty sleeping

Q: What mood and muscle findings occur in hyperthyroidism?

Irritability

Q: What nervous system, menstrual, weight, bowel, hand, tremor, and nail findings occur in hyperthyroidism?

Nervousness

Q: What is true about most signs of thyroid disease?

Most signs neither sensitive nor specific…

Q: What pulse findings may occur in thyroid disease?

Pulse – tachy, afib or bradycardic

Q: What hand findings may occur in thyroid disease?

Hands – pale skin, sweaty, trembling, or cold

Q: What eye findings may occur in thyroid disease?

Eyes – exophthalmos, proptosis, periorbital edema

Q: What miscellaneous findings may occur in thyroid disease?

Misc – thyroid acropachy, pretibial myxoedema, hyperactivity, restlessness, hyperlipidemia

Q: What is Hertogue’s sign?

Hertogue’s sign – (lateral eyebrow thinning)

Q: What are the sensitivity and specificity of Achilles Reflex Time?

Achilles Reflex Time – 77% sensitive / 93% specific

Q: What does prolonged relaxation phase of DTRs indicate?

(prolonged relaxation phase of DTRs)

Q: What has the highest specificity for all potential symptoms?

*Highest specificity for all potential symptoms

Q: What are the key symptoms of hypothyroidism?

Arthritis

Q: What are the key symptoms of hyperthyroidism?

Difficulty sleeping

Q: What is the major limitation of monitoring lone TSH?

To monitor “LONE” TSH has CRUCIAL LIMITATIONS . . .

Q: What correlates more closely with metabolic state?

METABOLIC STATE CORRELATES MORE CLOSELY WITH THE FREE CONCS OF THYROID HORMONES

Q: What are the analytical issues with thyroid labs?

ANALYTICAL ISSUES: FT4 (MOST RELIABLE) + TSH > FT3 + RT3 (T3 & FT3 ↑ VARIABILITY)

Q: What variability affects TSH interpretation?

GENETIC VARIABILITY

Q: How does TSH concentration change with age?

TSH conc ↑ with age (TSH ↑ by 1.0 μIU/mL Q 10 years after 50 yo)

Q: What fluctuations occur during T4 therapy?

TSH & T4 show fluctuations during stable T4 therapy that exceed analytical imprecision

Q: What defines meaningful change in TSH and FT4?

Meaningful “change” can be inferred when repeat measures exceed 50% (TSH) and 25% (FT4)

Q: What is difficult to define in many clinical scenarios?

DIFFICULT TO DEFINE NORMAL TSH REFERENCE RANGE FOR MANY CLINICAL SCENARIOS

Q: What are the uncertain “optimal” TSH reference ranges?

Am Assoc Clin Endo 0.3 – 3 μIU/mL

Q: What is true about T4 replacement and TSH targets?

T4 REPLACEMENT – OPTIMAL TARGET TSH DIFFERS FROM REFERENCE INTERVAL

Q: What is Desiccated Thyroid Extract (Armour Thyroid)?

“Cleaned, dried, powdered, porcine thyroid gland previously deprived of fat and connective tissue” AND protein-bound Iodine, AND other unmeasured compounds

Q: What non‑iodinated and iodinated components are in desiccated thyroid extract?

Non-iodinated (Calcitonin)

Q: What is the tablet strength and hormone content of desiccated thyroid extract?

Tablets = 65mg (1 grain)

Q: What is the T4/T3 ratio in porcine vs human thyroid?

T4 / T3 Ratio: 4.2 : 1 (porcine) vs 11-14 : 1 (human)

Q: What are the potential issues with desiccated thyroid extract?

Potential for supra-physiologic levels of T3

Q: What is the study title comparing DTE and levothyroxine?

Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study.

Q: What issue was observed when switching patients from DTE to L‑T4?

Patients previously treated with desiccated thyroid extract (DTE), when being switched to levothyroxine (L-T₄), occasionally did not feel as well despite adequate dosing based on serum TSH levels.

Q: Who were the study patients?

Patients (n = 70, age 18–65 years) w/ primary hypothyroidism on stable dose of L-T₄ for 6 months

Q: What was the study intervention?

Patients were randomized to either DTE or L-T₄ for 16 weeks and then crossed over for the same duration.

Q: What were the key results of the study?

No differences in symptoms and neurocognitive measurements. Patients lost 3 lb on DTE treatment (172.9 ± 36.4 lb vs 175.7 ± 37.7 lb, P < .001).

Q: What were patient preferences at the end of the study?

34 patients (48.6%) preferred DTE, 13 (18.6%) preferred L-T₄, and 23 (32.9%) had no preference.

Q: What did subgroup analysis show for patients who preferred DTE?

Those patients who preferred DTE lost 4 lb during the DTE treatment, and their subjective symptoms were significantly better while taking DTE (P < .001 for both).

Q: What is the study conclusion?

DTE therapy did not result in a significant improvement in quality of life

Q: What defines subclinical hypothyroidism (SCH)?

(Mild) ↑ TSH w/ normal FT4 (and FT3) concs (and no significant clinical symptoms)

Q: What increases the risk of conversion from SCH to overt hypothyroidism?

Risk of Conversion to “OVERT” → ↑ w/ severity ↑↑ TSH & TPOs

Q: When is typical SCH treatment recommended?

Pregnancy

Q: What cardiovascular risk is associated with SCH?

SCH → ↑ CVDz risk

Q: What is the prevalence range of SCH?

SCH prevalence ranges 3–20%

Q: What defines sub-clinical hypothyroidism?

Elevated TSH but normal T4 and T3 and patient may or may not be symptomatic (symptoms are few and mild)

Q: What is true about treating sub-clinical hypothyroidism?

Decision to treat is controversial

Q: What factors increase likelihood of treatment in overt hypothyroidism?

The higher the TSH and more symptomatic the more likely to need Rx