Approach to the Patient with Endocrine Disease

Most endocrine disorders are due to either an excess or a deficiency of a hormone that is transported in the systemic circulation and therefore result in multiorgan manifestations. Since individual hormones commonly have multiple sites of action, patients rarely present with a single set of symptoms or signs isolated to only one organ system. Generalized nonspecific symptoms such as weakness, difficulty concentrating, lack of energy, and change in appetite are common. Any single symptom evaluated in isolation is rarely helpful, and a constellation of findings is typically required to point to the correct diagnosis ( Table 202-1 ). Furthermore, as individuals age, many symptoms associated with deficiencies or excesses of hormones may change.

To diagnose an endocrinologic condition, a careful longitudinal history is critical. The duration of hormone excess or deficiency often dictates the severity of symptoms, and the characterization of progressive symptoms over time can be very helpful in selecting diagnostic tests, substantiating the need for treatment, and choosing the optimal treatment. The physical examination helps to confirm the likelihood of a diagnosis; for example, the presence of a symmetrically enlarged thyroid gland indicates that Graves disease is the most likely cause of hyperthyroidism ( Chapter 207 ). Even if endocrine disorders are diagnosed by biochemical screening in the absence of symptoms or signs of overt disease (e.g., hyperparathyroidism; Chapter 227 ), a thorough history and physical examination are still important to determine whether the patient is truly in the asymptomatic phase of the disease and whether observation or therapy is the preferred option. A careful temporal history of a symptomatic change may also assist with the differential diagnosis—for example, whether a thyroid mass is due to a hemorrhagic cyst (i.e., occurring suddenly) or is an adenoma that evolved over an extended period. A thorough general history and physical examination may identify diseases associated with endocrinologic abnormalities, such as cancers that secrete ectopic hormones.

An accurate family history can indicate a need for genetic testing or familial screening. A thorough evaluation of medication use is also mandatory. Some medications can mask the symptoms of overt endocrine disease, such as β-blockers in hyperthyroidism, and others can exacerbate the findings, such as use of a thiazide diuretic in hyperparathyroidism. Medications also may confound laboratory evaluation, such as diuretics in patients with hyperaldosteronism or acetaminophen in patients screened for pheochromocytoma; in such situations medications may need to be discontinued before testing. Finally, it may be difficult to obtain an accurate history of certain complaints. For example, in evaluating male sexual dysfunction ( Chapter 216 ), a corroborating history from his partner may be needed.

The off-target effects of treatments provide another example of the importance of a complete medical history. A variety of medical treatments also may cause either hormone excess or deficiency. For example, administration of high-dose glucocorticoid therapy for immune suppression can result in Cushing syndrome, and abrupt discontinuation of such therapy can cause acute adrenal insufficiency because of suppression of the pituitary-adrenal axis ( Chapter 208 ). Immunotherapy with checkpoint inhibitors ( Chapter 164 ) may cause both endocrine excess and deficiency, most commonly involving the thyroid gland. Many traditional chemotherapies adversely affect reproductive endocrine function, and radiation therapy ( Chapter 18 ) of tumors may cause endocrine deficiencies.