A 56-year-old woman comes to the physician with lethargy, weight loss, nausea, vomiting, and constipation for the past 2 months. She is 3 years postmenopausal and has no long-standing medical problems. The patient currently takes no prescription medications and does not use tobacco or alcohol. Her family history is positive for osteoporosis and hypertension. Her blood pressure is 124/66 mm Hg and pulse is 64/min. She weighs 63 kg (138 lb) and is 160 cm (5' 3") tall. Her body mass index is 24.4 kg/m². The patient appears mildly pale. The thyroid gland is normal to palpation. Heart and lung sounds are normal. Abdominal examination is unremarkable. Neurologic examination shows prolonged relaxation time of the ankle reflexes. Laboratory results are as follows: Red blood cells are normochromic and normocytic. The 8:00 AM serum cortisol is 7 µg/dL (normal 5-20 µg/dL) . Repeat thyroid function tests show similar results.
Which of the following is the most appropriate next step in evaluation of this patient?

Question

A 56-year-old woman comes to the physician with lethargy, weight loss, nausea, vomiting, and constipation for the past 2 months. She is 3 years postmenopausal and has no long-standing medical problems. The patient currently takes no prescription medications and does not use tobacco or alcohol. Her family history is positive for osteoporosis and hypertension. Her blood pressure is 124/66 mm Hg and pulse is 64/min. She weighs 63 kg (138 lb) and is 160 cm (5' 3") tall. Her body mass index is 24.4 kg/m². The patient appears mildly pale. The thyroid gland is normal to palpation. Heart and lung sounds are normal. Abdominal examination is unremarkable. Neurologic examination shows prolonged relaxation time of the ankle reflexes. Laboratory results are as follows:

Red blood cells are normochromic and normocytic. The 8:00 AM serum cortisol is 7 µg/dL (normal 5-20 µg/dL) . Repeat thyroid function tests show similar results.
Which of the following is the most appropriate next step in evaluation of this patient?

Quizplus · Accepted Answer

Explanation: 11ec2b69_c13b_44fe_8f63_6925c27da4d7_MD0005_00 This patient most likely has central hypothyroidism, as suggested by typical clinical features, low serum sodium, borderline low thyroid-stimulating hormone (TSH), and low free T4 levels. Low thyroid hormone levels should cause a substantial increase in the level of TSH. However, in this patient, the low free T4 is not accompanied by elevated TSH, strongly suggesting hypothalamic or pituitary disease. The pituitary gland secretes several hormones, and central hypothyroidism should prompt additional biochemical assessments and pituitary imaging (magnetic resonance imaging preferred). The mild hyponatremia may be due to hypothyroidism (decreased renal water clearance), but the borderline-low 8:00 AM cortisol and glucose suggest concomitant central adrenal insufficiency. Measurement of baseline adrenocorticotropic hormone (ACTH) levels and a short ACTH (cosyntropin, synthetic ACTH) stimulation test would be the most practical methods to assess adrenal reserve. All patients with primary adrenal insufficiency will have a subnormal increase in cortisol following ACTH stimulation. Most patients with central adrenal insufficiency will also have a subnormal response to ACTH stimulation due to adrenal atrophy from chronic ACTH deficiency. A low serum ACTH level with a subnormal response to ACTH confirms central adrenal insufficiency. If there is still concern for central adrenal insufficiency after a normal ACTH stimulation test, the hypothalamic-pituitary-adrenal axis can be further assessed with a metyrapone test or insulin-induced hypoglycemia test (flow chart). Levothyroxine treatment for hypothyroidism in patients with uncorrected adrenal insufficiency may trigger adrenal crisis by increasing metabolic demand and clearance of glucocorticoids. (Choice B) Antithyroid antibodies are useful in the evaluation of goiter and primary hypothyroidism (eg, Hashimoto thyroiditis/chronic autoimmune thyroiditis) but would not be helpful in suspected central hypothyroidism. (Choice C) Measuring reverse T3 (rT3), particularly in a hospitalized patient, is sometimes done to distinguish euthyroid sick syndrome from central hypothyroidism, as it is elevated in euthyroid sick syndrome but low in hypothyroidism. But rT3 levels may be normal or even elevated in some patients with mild central hypothyroidism, which limits the clinical utility of this test. Also, there is often a substantial delay in reporting of this test, which further limits its usefulness. (Choice D) T3 assay has a limited role in the evaluation of hypothyroid patients as the circulating T3 levels are in the normal range in the majority of patients. In addition, circulating T3 levels may decrease substantially in nonthyroidal illnesses (sick euthyroid syndrome). (Choice E) Thyroglobulin level is useful in the follow-up management of patients with differentiated thyroid cancers and in the evaluation of those with suspected factitious thyrotoxicosis. Educational objective: Central hypothyroidism is characterized by low thyroid hormone levels with low or low-normal thyroid-stimulating hormone. Central hypothyroidism should prompt assessment of other pituitary hormones as well as pituitary imaging (magnetic resonance imaging). References: Clinical review: central hypothyroidism: pathogenic, diagnostic, and therapeutic challenges. (http://www.ncbi.nlm.nih.gov/pubmed/22851492)

A 56-Year-Old Woman Comes to the Physician with Lethargy, Weight