The aim of the question is to help gain understanding of the role of free (nonprotein bound) thyroid hormone in regulating TSH secretion. The hypothalamo-pituitary unit “reads” the free hormone level, not the total hormone level, which is subject to changes owing to alterations in protein binding (thyroxine-binding globulin, thyroid-binding prealbumin, albumin, or conditions that may interfere with binding).

In practice, the free thyroxine index can be calculated from total T₄ and an estimate of protein binding (T₄U or T₃RU; T₄U measures binding directly, whereas T₃RU provides an index of unbound hormone). Automated FT₄ assays are replacing these more indirect indices; the gold standard, FT₄ by equilibrium dialysis, is available in some reference laboratories but is rarely needed. Thus, serum TSH in this patient should provide the best indicator of thyroid function status and is independent from thyroid hormone protein-binding abnormalities.

Although TSH secretion may be acutely altered by stress, illness, or drugs, the major regulation is based on the integrated thyroid hormone exposure over the preceding 2 to 5 weeks. Although iron preparations and aluminumcontaining compounds can interfere with T₄ absorption, the elevated serum T₄ level argues against this notion. Similarly, a progressive loss of thyroid function would be expected to lead to low or low-normal T₄ values. Although acquired thyroid hormone resistance may occur hypothetically, no clinical descriptions of such disorders exist. The correct answer is not a rare occurrence: Patients often want to please their health care provider, even if it means not being perfectly honest on occasion.

This question reinforces the clinical presentation of elderly patients with thyrotoxicosis and their management. Although weight loss despite a generous appetite is characteristic in the younger adult, anorexia is not an uncommon finding in the elderly. Cachexia in an “apathetic” patient should be considered. (Concomitant Addison disease in a patient with known thyroid autoimmunity is a “distractor” in the current case presentation; the lack of pigmentation was intended to get the reader back on focus.) A cardiac dysrhythmia or congestive heart failure may be the major feature(s). The most common cause of hyperthyroidism in this age group is toxic multinodular goiter (sometimes iodide induced), but the absence of a goiter may be seen in up to 25% of elderly patients (5% in young adults).

Serum T₃ may be of academic interest (and occasionally a higher T₄:T₃ ratio may help discriminate thyroiditis or toxic multinodular goiter from Graves hyperthyroidism), but it is generally reserved for cases in which total T₄ and FT₄ values are normal. Thyroid-stimulating antibodies are of minor value in ruling out Graves disease (usually a positive family history is obtained), but this diagnosis can be inferred from an elevated RAIU and diffuse scan order. Thyroid microsomal antibodies are a less expensive but less specific surrogate for Graves disease. The RAIU is necessary to discriminate thyroid hyperfunction (autonomous nodule[s], receptor antibody, TSH, or human chorionic gonadotropin driven) from subacute or silent thyroiditis, iatrogenic, or factitious causes. (Recent exposure to radiocontrast media or iodine-containing drugs or pregnancy may preclude its use, however.) A scan is of particular value when the clinician is unsure of the size and nature of the thyroid gland.

β-Blockers and propylthiouracil are helpful as primary therapy for hyperthyroidism in the elderly. Propylthiouracil is initiated only after the diagnosis is confirmed by a radioactive iodine uptake (and scan, if necessary). Radioactive iodine therapy may cause a transient worsening (radiation thyroiditis) of the hyperthyroidism and is often postponed in elderly patients until euthyroidism is attained (and antithyroid medication transiently withdrawn for 2 to 3 days before ¹³¹I treatment). β-Blockers and digoxin are helpful in controlling the heart rate in atrial fibrillation. Patient has a CHADS2 score of 3, and Coumadin is indicated in preventing embolic consequences of atrial fibrillation. The only drug not indicated without more data (the patient was not in “thyroid storm”) is the glucocorticoid.

Risk factors for DM include family history, obesity, hypertension, and hypokalemia. The diagnostic criteria for the diagnosis of DM include

Diagnostic criteria 1 to 3 above should be confirmed with repeat testing on a separate occasion.

Glyburide should not be discontinued but could be reduced. With an elevated creatinine, metformin should not be prescribed. One should start a patient on acarbose (Precose), slowly and gradually increasing dosage. Rosiglitazone could be used, starting at 4 mg daily.

This case illustrates the differences between primary and secondary adrenal insufficiency in clinical presentation and treatment. In secondary adrenal insufficiency, the renin-aldosterone axis is intact; therefore, hyperkalemia and metabolic acidosis are not seen, and fludrocortisone is not required for treatment.

This case illustrates secondary adrenal insufficiency and inadequate glucocorticoid replacement. Physiologic hydrocortisone replacement is 20 to 30 mg daily. No data suggest the need for desmopressin or increased testosterone. Levothyroxine doses should not be adjusted by the TSH in secondary disease.

Generally, the 24-hour urine free cortisol is the best screening test; the 1-mg ODST is easier to perform but has more false-positive results, including increased cortisol-binding globulin owing to the estrogen in oral contraceptives. Radiographic imaging is not indicated until the diagnosis is established biochemically.

This patient likely has adrenal insufficiency from an adrenal hemorrhage through the potentiation of warfarin by ASA. Intravenous fluids and dexamethasone can be lifesaving; then other options can be considered. Dexamethasone does not cross react with cortisol in the radioimmune assay. All choices are reasonable, but answer c should be performed first.

Biochemical testing should be influenced by clinical findings. Even if no evidence of hormone production is apparent through history and physical examination, a biochemical screening for pheochromocytoma should nonetheless be done. A 1-mg overnight dexamethasone suppression test should also be done on all patients to exclude subclinical Cushing syndrome.

Surgery is not recommended for incidental adrenal masses unless they are large (>4 to 6 cm). A FNA biopsy can be diagnostic but should be used only when an immediate answer is needed and an experienced radiologist is available. FNA biopsy can diagnose metastatic disease but cannot always distinguish adrenal carcinoma from adenoma. Conventional MRI cannot distinguish metastasis from adenoma; only opposed-phase imaging (chemical-shift imaging) can do this. When CT or MRI cannot provide a definite diagnosis (metastasis versus adenoma), follow-up CT is indicated.

The low T₄ along with an inappropriately normal TSH level in an individual who is clinically hypothyroid should prompt a search for hypothalamic-pituitary dysfunction most commonly secondary to a pituitary tumor. Treatment of hypothyroidism in a patient with adrenal insufficiency may result in worsening of adrenal insufficiency symptoms due to an increase in metabolism of an already low cortisol level and should be approached with caution.