The initial methimazole treatment was appropriate and preferable to propylthiouracil because of its longer duration of action allowing once daily dosing and its improved safety profile. JP presents with the typical signs and symptoms of hypothyroidism following RAI despite levothyroxine replacement. Either radioactive iodine or thyroidectomy are reasonable and effective strategies for definitive treat-ment of her hyperthyroidism, especially before becoming pregnant to avoid an acute hyperthyroid exacerbation during pregnancy or following delivery. Her hypothy-roid symptoms should have been easily corrected by the addition of levothyroxine dosed correctly at 1.7 mcg/kg/ day or 100 mcg daily. Because she is young and has no cardiac disease, full replacement doses were appropriate to start. However, her elevated TSH level indicates inad-equate levothyroxine replacement which may be related to nonadherence, or concomitant calcium and omeprazole co-administration. For optimal absorption, levothyroxine should be taken orally 60 minutes before meals on an empty stomach or at bedtime, and separated by 4 hours from her calcium administration. Lower thyroxine doses may also be sufficient if her omeprazole is stopped. Once weekly thyroxine injections may be effective in those with ongoing nonadherence. Thyroid function tests should be monitored after 6–8 weeks of therapy, obtained before thyroxine administration to avoid transient hormone alter-ations, and the dosage adjusted to achieve a normal TSH level and resolution of hypothyroid symptoms.
George P. Chrousos, MD
A 19-year-old man complains of anorexia, fatigue, dizziness, and weight loss of 8 months’ duration. The examining physician discovers postural hypotension and moderate vitiligo (depigmented areas of skin) and obtains routine blood tests. She finds hyponatremia, hyperkalemia, and acidosis and suspects Addison’s disease. She performs a standard ACTH 1–24 stimulation test, which reveals an insufficient plasma cortisol response compatible with primary adrenal insuf-ficiency. The diagnosis of autoimmune Addison’s disease is made, and the patient must start replacement of the hormones he cannot produce himself. How should this patient be treated? What precautions should he take?
The natural adrenocortical hormones are steroid molecules produced and released by the adrenal cortex. Deficiency of the adrenocortical hormones results in the signs and symptoms of Addison’s disease. Excess production causes Cushing’s syndrome. Both natural and synthetic corticosteroids are used for the diagnosis and treatment of disorders of adrenal function. They are also used—more often and in much larger doses—for treatment of a variety of inflammatory and immunologic disorders.
Secretion of adrenocortical steroids, especially the glucocorticoids, is controlled by the pituitary release of corticotropin (ACTH) (see Chapter 37). Corticotropin is derived from a larger protein synthesized in the pituitary, pro-opiomelanocortin (POMC). Secretion of the salt-retaining hormone aldosterone is primarily under the influence of circulating angiotensin and potassium. Corticotropin has some actions that do not depend on its effect on adrenocortical secretion. However, its pharmacologic value as an anti-inflammatory agent and its use in testing adrenal function depend on its secretory action. Its pharmacology is reviewed only briefly here.
Inhibitors of the synthesis or antagonists of the action of the adrenocortical steroids are important in the treatment of several conditions. These agents are described at the end of this chapter.