Medicine Marrow Pg No 895-904 (Endocrinology)

Thyroid Follicle

• The thyroid follicle is the functional and structural unit of the thyroid gland.
• The follicular epithelial cells line the follicle and are responsible for hormone production.
• Colloid is the material within the follicle that contains thyroglobulin, a protein that stores thyroid hormone precursors.
• Thyroglobulin is formed by the 29th day of gestation and is the first hormone precursor.
• Hormone synthesis begins by the 11th week of gestation.
• Thyroid-stimulating hormone (TSH) from the pituitary gland stimulates the production of thyroid hormones T3 and T4.
• Parafollicular/C-cells in the thyroid secrete calcitonin.
• Transcription factors like TTF-1, TTF-2, PAX-8, and PROP-1 are crucial for thyroid gland development.
• Deficient TSH (as in hypopituitarism) can result in minimal to no hypothyroidism.

Basics of Thyroid Gland

• ¹³¹I is used for radioablation in Grave's disease.
• ¹²³I is used for brachytherapy.
• The recommended daily intake (RDA) of iodine is 150 µg/day for adults, 220 µg/day for pregnant women.
• Repleting iodine levels require a daily urinary excretion of iodine >100 µg.

Deiodinase Enzyme

• Di-type II (most abundant) is the primary enzyme for peripheral conversion of T4 to T3.
• Deiodinase inhibitors include propylthiouracil, amiodarone, steroids, and propranolol.

SICK EUTHYROID SYNDROME / LOW T3 SYNDROME

• Thyroid function tests (TFTs) should not be performed in patients with critical illness, systemic illness, or fasting for a few days.
• Deiodinase type 1 (D1) is inhibited and Deiodinase type 3 (D3) is activated in this syndrome.
• The stages of the syndrome are:
  • Early stage: Increased T4, normal T3, and increased reverse T3 (rT3)
  • Middle stage: Decreased TSH, increased rT3, decreased T3, increased T4.
  • Late stage: Rapid catabolism of all hormones, decreased T4, decreased TSH, decreased rT3, decreased T3.

Hormone Synthesis and Release

• TSH binds to the TSH receptor on the thyroid gland.
• Organification, iodination, and coupling are key steps in thyroid hormone synthesis.
• The final hormones T3 and T4 are released from the thyroid gland in a ratio of 10:1.
• T4 is converted peripherally to T3, the active form, accounting for 80% conversion and 20% synthesis.

Osteoporosis

• Osteoporosis is a loss of bone strength caused by a defect in bone quantity and quality.
• The earliest symptom is back pain.
• Postmenopausal women have the highest prevalence of osteoporosis.
• Most characteristic symptoms include fractures (neck of femur, hip bone, vertebral fracture, Colles' fracture).
• Distal forearm fractures are a sensitive marker of bone fragility in men.

Thyroid Function Tests

• Increased T3 and T4 levels constitute hyperthyroxinemia.
• Increased free T3 and free T4 levels indicate thyrotoxicosis.
• Thyroid function tests are not recommended in critically ill patients.

Thyroid Function and Body Processes

• Thyroid hormones regulate the basal metabolic rate (BMR), cardiac actions, oxygen utilization, and heart rate.
• Hypothyroidism causes a decrease in BMR, while hyperthyroidism causes an increase.
• Hypothyroidism can contribute to insulin resistance, hypercholesterolemia, menorrhagia, infertility, myopathy, osteopenia, and osteoporosis.
• Hyperthyroidism can cause hypercalcemia, hypercalciuria, and kidney stones.

Endocrinology

• Many conditions can result in secondary hypothyroidism including:
  • GI disease (e.g., celiac disease)
  • Hypogonadal states (e.g., hyperprolactinemia, Turner's syndrome, Klinefelter syndrome)
  • Rheumatological causes (e.g., ankylosing spondylitis, rheumatoid arthritis, sarcoidosis)
  • Endocrine causes (e.g., Cushing disease, hyperparathyroidism, diabetes insipidus, acromegaly, thyrotoxicosis)
  • Inherited diseases (e.g., porphyria, hemochromatosis, homocystinurea, Marfan's, sickle cell anemia, hemophilia)

Management of Osteoporosis

• Supportive care includes smoking cessation, Vitamin D3 intake, calcium intake, and increased physical activity.
• Bisphosphonates are the first choice for antiresorptive therapy.
• Denosumab is a RANK-L inhibitor used as a third-line therapy.
• Teriparatide and Abaloparatide are recombinant PTH therapies.
• Other drugs that may help manage osteoporosis include hormone replacement therapy, strontium ranelate, calcitonin, raloxifene, and newer medications like odanacatib, saracatinib, and romosozumab.

Basics of Thyroid Gland

• The thyroid gland is the first endocrine organ to form during embryonic development (3-4 weeks of gestation) and is derived from the endoderm.
• It migrates from the floor of the primitive pharynx to the anterior of the trachea.
• The blood supply is from the superior thyroid artery and the inferior thyroid artery.
• The recurrent laryngeal nerves (right and left) are located close to the inferior thyroid artery.
• The thyroid gland is innervated by the superior laryngeal nerve.

Thyroglossal Cyst

• Thyroglossal cysts are remnants of the thyroglossal duct that persist beyond 5 weeks of gestation.
• The location is often subhyoid, which is the most common position.
• Thyroglossal cysts can protrude with tongue movement and deglutition.
• The cyst can move upward and backward when the tongue protrudes.
• The cyst has a pseudocapsule formed by pretracheal fascia.

Supportive care and Drug used:

• Supportive care for osteoporosis includes smoking cessation, calcium intake, vitamin D3, and increased physical activity.
• Bisphosphonates are the first choice for antiresorptive therapy of osteoporosis.
• Oral bisphosphonates include Alendronate and Risedronate.
• Denosumab is a RANK-L inhibitor used as a third-line therapy.
• Teriparatide and Abaloparatide are recombinant PTH therapies.
• Other drugs that may help manage osteoporosis include hormone replacement therapy, strontium ranelate, calcitonin, raloxifene, and newer medications like odanacatib, saracatinib, and romosozumab.
• Zoledronate and Ibandronate are used for definitive care.

Thyroid Function Tests

• TFTs should always check for free T3 (fT3) and free T4 (fT4).
• The normal TSH range is 0.5- 5 mIU/L.
• Drug-induced changes to TFTs may require adjustments to medications and dosages:
  • Deiodinase inhibitors (e.g., propylthiouracil, amiodarone, steroids, Propranolol)
  • lodine (e.g., amiodarone, propylthiouracil)
  • Enzyme inducers (e.g., phenytoin, carbamazepine, rifampicin)
  • Drugs that reduce hormone absorption (e.g., aluminum hydroxide, cholestyramine, calcium carbonate, ferrous sulfate)
  • Drugs with effects on thyroid function (e.g., sertraline, ritonavir).