Thyroid Disorder : Definition, Pathophysiology, Diagnosis, And Treatment

Monday, February 24th 2014. | Disease

Thyroid Disorder, Definition, Pathophysiology, Diagnosis, and Treatment

Thyroid disorders encompass a variety of disease states affecting thyroid hormone production or secretion that result in alterations in metabolic stability. Hyperthyroidism and hypothyroidism are the clinical and biochemical syndromes resulting from increased and decreased thyroid hormone production, respectively.

Pathophysiology of Thyroid Disorder :
  • Thyrotoxicosis results when tissues are exposed to excessive levels of T4, T3, or both.
  • TSH-secreting pituitary tumors release biologically active hormone that is unresponsive to normal feedback control. The tumors may co-secrete prolactin or growth hormone; therefore, patients may present with amenorrhea, galactorrhea, or signs of acromegaly.
  • In Graves’ disease, hyperthyroidism results from the action of thyroid-stimulating antibodies (TSAb) directed against the thyrotropin receptor on the surface of the thyroid cell. These immunoglobulin G (IgG) antibodies bind to the receptor and activate the enzyme adenylate cyclase in the same manner as TSH.
  • An autonomous thyroid nodule (toxic adenoma) is a discrete thyroid mass whose function is independent of pituitary control. Hyperthyroidism usually occurs with larger nodules (i.e., those greater than 4 cm in diameter).
  • In multinodular goiters (Plummer’s disease), follicles with a high degree of autonomous function coexist with normal or even nonfunctioning follicles. Thyrotoxicosis occurs when the autonomous follicles generate more thyroid hormone than is required.
Diagnosis of Thyroid Disorders:
  • An elevated 24-hour radioactive iodine uptake (RAIU) indicates true hyperthyroidism: the patient’s thyroid gland is overproducing T4, T3, or both (normal RAIU 10% to 30%). Conversely, a low RAIU indicates that the excess thyroid hormone is not a consequence of thyroid gland hyperfunction.
  • TSH-induced hyperthyroidism is diagnosed by evidence of peripheral hypermetabolism, diffuse thyroid gland enlargement, elevated free thyroid hormone levels, and elevated serum immunoreactive TSH concentrations. Because the pituitary gland is extremely sensitive to even minimal elevations of free T4, a detectable TSH level in any thyrotoxic patient indicates inappropriate production of TSH.
  • TSH-secreting pituitary adenomas are diagnosed by demonstrating lack of response to TRH stimulation, elevated TSH α-subunit levels, and radiologic imaging.
  • In thyrotoxic Graves’ disease, there is an increase in the overall hormone production rate with a disproportionate increase in T3 relative to T4. Saturation of TBG is increased due to the elevated levels of serum T4 and T3, which is reflected in an elevated T3 resin uptake. As a result, the concentrations of free T4, free T3, and the free T4 and T3 indices are increased to an even greater extent than are the measured serum total T4 and T3 concentrations. The TSH level is undetectable due to negative feedback by elevated levels of thyroid hormone at the pituitary. The diagnosis of thyrotoxicosis is confirmed by measurement of the serum T4 concentration, T3 resin uptake (or free T4), and TSH. An increased 24-hour RAIU (obtained in nonpregnant individuals) documents that the thyroid gland is inappropriately using the iodine to produce more thyroid hormone when the patient is thyrotoxic.
  • Toxic adenomas may result in hyperthyroidism with larger nodules. Because there may be isolated elevation of serum T3 with autonomously functioning nodules, a T3 level must be measured to rule out T3 toxicosis if the T4 level is normal. After a radioiodine scan demonstrates that the toxic thyroid adenoma collects more radioiodine than the surrounding tissue, independent function is documented by failure of the autonomous nodule to decrease its iodine uptake during exogenous T3 administration.
Treatment of Thyroid Disorders:
  • Surgical removal of the thyroid gland is the treatment of choice for coexisting cold nodules, extremely large goiters, lack of remission on antithyroid drug treatment, and patients with contraindications to thionamides (i.e., allergy or adverse effects) and RAI (i.e., pregnancy).
  • If thyroidectomy is planned, PTU or methimazole is usually given until the patient is biochemically euthyroid (usually 6 to 8 weeks), followed by the addi- tion of iodides (500 mg/day) for 10 to 14 days before surgery to decrease the vascularity of the gland. Levothyroxine may be added to maintain the euthyroid state while the thionamides are continued.
  • Propranolol has been used for several weeks preoperatively and 7 to 10 days after surgery to maintain a pulse rate less than 90 beats/min. Combined pretreatment with propranolol and 10 to 14 days of potassium iodide also has been advocated.
  • Complications of surgery include persistent or recurrent hyperthyroidism (0.6% to 18%), hypothyroidism (up to about 49%), hypoparathyroidism (up to 4%), and vocal cord abnormalities (up to 5%). The frequent occurrence of hypothyroidism requires periodic follow-up for identification and treatment.

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