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Diagnosis

Thyroid nodules are common and are often found incidentally on imaging tests. When a nodule is discovered, assess thyroid function with a serum TSH level.

A low TSH level suggests a benign, autonomously functioning thyroid adenoma. If TSH is suppressed, order a radioisotope scan to confirm the diagnosis and to rule out additional nonfunctioning nodules within a multinodular goiter. The serum TSH level is normal (and unhelpful) in most other patients with thyroid nodules.

Endocrinology and Metabolism

Thyroid ultrasonography allows for accurate detection and sizing of all nodules on the thyroid gland, and ultrasound character- istics can be used to further delineate cancer risk.

Look for risk factors for thyroid cancer, including family history of thyroid malignancy, personal history of radiation therapy to the head and neck, or other radiation exposure in childhood.

FNAB is indicated for:

• all thyroid nodules >1 cm associated with a normal TSH level

• nodules <1 cm in patients with risk factors for thyroid cancer or suspicious ultrasound characteristics

The risk for malignancy is the same for multiple nodules in a multinodular goiter as it is for a solitary nodule; therefore, the evaluation and management is identical. Biopsy should be performed on the three or four nodules (>1 cm) with the most suspi- cious ultrasound features. In the absence of suspicious features, the largest nodules should be chosen for aspiration. Evaluate patients with multinodular goiter for compressive symptoms:

• dysphagia • hoarseness

• dyspnea (tracheal compression from substernal goiter)

Consider evaluation with barium swallow, direct vocal cord visualization, spirometry with flow volume loops, and/or chest CT as needed.

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◆Don’t Be trickeD

• Serum thyroglobulin measurement is not helpful in distinguishing benign and malignant thyroid nodules.

• Calcitonin measurement is only considered in patients with hypercalcemia or a family history of thyroid cancer or MEN2.

Therapy

Follow benign nodules with periodic ultrasonography. Although benign thyroid nodules usually remain stable or decrease in size, one third may increase in size. Malignancy must be ruled out when a nodule increases in size or if a nodule develops con- cerning ultrasound characteristics.

Treat hyperfunctioning solitary thyroid nodules with radioac- tive iodine ablation or hemithyroidectomy.

Surgery is indicated for patients with continued nodule growth despite normal initial FNAB results or nondiagnostic results on repeat FNAB and for patients with malignant cytology. Surgery is also indicated for large multinodular goiters associated with compressive symptoms.

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◆Don’t Be trickeD

• Do not prescribe T4-suppression therapy for benign

thyroid nodules.

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❖test Yourself

An 18-year-old man has a 2-cm right-sided thyroid nodule. The serum TSH level is 1.4 μU/mL.

ANSWER: Perform an FNAB.

Thyroid Nodule: A hyperfunctioning nodule is shown on the lateral aspect of the

left thyroid lobe on thyroid scan.

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Endocrinology and Metabolism

Hypercortisolism (Cushing Syndrome)

Diagnosis

The most common cause of Cushing syndrome is the use of glucocorticoids (systemic, topical, intra-articular, or inhaled). Doses of prednisone (or equivalent) ≤5 mg/d are unlikely to cause clinically significant hypothalamic-pituitary-adrenal axis sup- pression, while those >10-20 mg/d can cause hypothalamic-pituitary-adrenal axis suppression after ≥3 weeks of consecutive use.

Endogenous causes of Cushing syndrome can be ACTH-dependent or ACTH-independent. ACTH-dependent causes of Cushing syndrome is defined by ACTH levels elevated or inappropriately “normal” for level of cortisol:

• ACTH-secreting pituitary adenomas (Cushing disease) • ACTH-secreting carcinomas and carcinoid tumors

ACTH-independent causes of Cushing syndrome is defined by low or “normal” ACTH levels for level of cortisol:

• Adrenal adenomas • Adrenal carcinomas

Clinical findings that are highly specific for Cushing syndrome include:

• centripetal obesity • facial plethora

• supraclavicular or dorsocervical (“buffalo hump”) fat pads • wide (>1 cm) violaceous striae

First-line diagnostic studies include:

• low-dose dexamethasone suppression test (failure to suppress serum cortisol to <5 μg/dL)

• 24-hour urine cortisol level (elevated) • late night salivary cortisol level (elevated)

If cortisol level is elevated (or not suppressible), order an ACTH level to differentiate ACTH-dependent from ACTH-independent hypercortisolism.

StUDY tABLe: Evaluation of Hypercortisolism

If you see this… Do this…

Morning ACTH elevated (>20 pg/mL) Pituitary MRI or CT Morning ACTH suppressed or normal (<5 pg/mL) Adrenal CT

If ACTH is elevated but no pituitary tumor is visualized, perform high-dose (8-mg dexamethasone) suppression test to differ- entiate between pituitary and ectopic tumor ACTH production.

If high-dose dexamethasone does not suppress cortisol production, an ectopic tumor is releasing ACTH. The most common ACTH-secreting malignant tumors are SCLC, bronchial carcinoid, pheochromocytoma, and medullary thyroid carcinoma. Begin investigation with chest and abdomen CT.

If high-dose dexamethasone suppresses pituitary ACTH production and adrenal cortisol secretion, the source is the pituitary. In this case, obtain intrapetrosal sinus sampling for ACTH to confirm pituitary source.

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◆Don’t Be trickeD

• False-positive results (failure to suppress cortisol) with the 1-mg dexamethasone suppression test are commonly due to alcohol use, obesity, and psychological disorders.

Endocrinology and Metabolism

Therapy

Surgical resection of the adrenal gland, pituitary gland, or ectopic tumor is the optimal therapy for Cushing syndrome. Bisphosphonates are the treatment of choice for low bone den- sity caused by hypercortisolism.

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❖test Yourself

A 43-year-old woman has diabetes mellitus, hypertension, hirsutism, and central obesity. The serum cortisol level is 26 μg/dL after administration of 1 mg of dexamethasone and 8.2 μg/dL after 8 mg of dexamethasone. The serum ACTH level is 50 pg/mL.

ANSWER: The diagnosis is a pituitary tumor. Select

pituitary gland MRI.