Key points include: Advances and more frequent use of diagnostic radiology have led to the increased prevalence of endocrine incidentalomas; Pituitary, thyroid, and adrenal incidentalomas must be assessed for dysfunctional hormone secretion and malignant potential; Inpatient management of endocrine incidentalomas should include consultation of endocrine or surgical teams in cases of dysfunctional or malignant lesions; Post-discharge instructions shouldclearly delineate timelines for repeat imaging, laboratory testing, and subspecialist follow-up.
by Darlene Tad-y, MD, Section of Hospital Medicine, University of Colorado Denver
Case
A 54-year-old man with a history of hypertension treated with hydrocholorothiazide and Type 2 diabetes mellitus is admitted with abdominal pain and found to have an incidental 2.1-cm left adrenal mass on CT scan of the abdomen. He denies symptoms of headache, palpitations, weight gain, or muscle weakness. His exam is significant for mildly elevated blood pressure. What is the best approach for evaluation and management of this incidental finding?
Overview
Incidentalomas are mass lesions that are inadvertently discovered during radiolographic diagnostic testing or treatment for other clinical conditions that are unrelated to the incidental mass. In recent decades, improvements in radiographic diagnostic techniques and sensitivity have led to increasing discovery of incidental lesions that are often in the absence of clinical signs or symptoms.1 Three commonly discovered lesions by hospitalists are pituitary, thyroid, and adrenal incidentalomas.2 The concerns associated with these findings relate to the potential for dysfunctional hormone secretion or malignancy.
Patients found with pituitary incidentalomas can be susceptible to several types of adverse outcomes: hormonal hypersecretion, hypopituitarism, neurologic morbidity due to tumor size, and malignancy in rare cases. Thyroid incidentalomas are impalpable nodules discovered in the setting of ultrasound or cross-sectional neck scans, such as positron emission tomography (PET) scans. Discovery of a thyroid incidentaloma raises concern for thyroid malignancy.3 The increased use of abdominal ultrasound, CT scans, and MRI has fueled the growing incidence of adrenal incidentalomas (AIs).
The discovery of an endocrine incidentaloma in the inpatient setting warrants a systematic approach that includes both diagnostic and potentially therapeutic management. A hospitalist should consider an approach that includes (see Table 1):
- Characterization of the incidentaloma, including clinical signs and symptoms, size, hormonal function, and malignant potential;
- Immediate management, including medical versus surgical treatment; and
- Post-discharge management, including monitoring.
Review of the Data
Pituitary incidentalomas. The prevalence of pituitary incidentalomas found by CT ranges from 3.7% to 20%, while the prevalence found by MRI approximates 10%. Autopsy studies have revealed a prevalence ranging from 1.5% to 26.7% for adenomas less than 10 mm, considered to be microadenomas. Broad categories of etiologies should be considered: pituitary adenoma, nonpituitary tumors, vascular lesions, infiltrative disorders, and others (see Table 2). The majority of pituitary adenomas secrete prolactin (30% to 40%) or are nonsecreting (30% to 40%). Adenomas secreting adrenocorticotropin hormone (ACTH, 2% to 10%), growth hormone (GH, 2% to 10%), thyroid-stimulating hormone (TSH, <1%), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) are much less common.2 Significant morbidity and premature mortality are associated with hyperprolactinemia, acromegaly (growth hormone excess), Cushing’s syndrome, and hyperthyroidism. Additionally, up to 41% of patients with macroadenomas were found to have varying degrees of hypopituitarism due to compression of the hypothalamus, the hypothalamic-pituitary stalk, or the pituitary itself.4
Recently, the Endocrine Society released consensus recommendations to guide the evaluation and treatment of pituitary incidentalomas, which are included in the approach outlined below.5 A detailed history and physical examination should be obtained with specific inquiry as to signs and symptoms of hormonal excess and mass effect from the tumor. Examples of symptoms of hormone excess can include:
- Prolactin: menstrual irregularity, anovulation, infertility, decreased libido, impotence, osteoporosis;
- Growth hormone: high frequency of colonic polyps and colon cancer (chronic excess);
- TSH: thyrotoxicosis, atrial fibrillation; and
- ACTH: hypertension, osteoporosis, accelerated vascular disease.
Symptoms related to the mass effect of the tumor include visual field defects and hypopituitarism related to the deficient hormone, including:
- FSH/LH: oligomenorrhea, decreased libido, infertility;
- TSH: hypothyroidism (weight gain, constipation, cold intolerance);
- ACTH: adrenal insufficiency (hypotension, hypoglycemia, weight loss); and
- ADH: polyuria, polydypsia.
The size and location of the pituitary lesion must be assessed. Lesions greater than 10 mm are considered macroademonas, and their size will affect their management. If the lesion was initially identified by CT scan, an MRI is recommended to better evaluate it.5 If the MRI locates the incidentaloma abutting the optic nerve or chiasm, then the patient should undergo a formal visual field examination.
Indications for an inpatient surgical referral for treatment include: a lesion larger than 2 cm, evidence of mass effect such as visual field defects, neurologic compromise, opthalmoplegia, hypopituitarism, a tumor abutting the optic nerve or chiasm, pituitary apoplexy, and hypersecretion of hormones other than prolactin. Patients with prolactinomas warrant an inpatient endo-crinology consult and may need medical management with a dopamine agonist. Hormone replacement therapy can also be provided for patients with hypopituitarism.2,5
For patients who do not meet the criteria for inpatient surgical therapy, follow-up management must be arranged at the time of discharge. Clinical, laboratory assessment, and an MRI should be scheduled six months after the initial finding of the incidentaloma with the patient’s PCP or with an endocrinologist.5
Thyroid incidentalomas. The prevalence of thyroid nodules based on ultrasound studies ranges from 19% to 46%, with autopsy studies estimating an incidence of approximately 50%.2,6 Incidence of thyroid nodules also increases with age, as almost 60% of people over the age of 60 harbor a thyroid incidentaloma. The rate of malignancy in the general population has ranged between 8% and 24%; however, in the last decade, the rates have increased by 2.4 times as more sophisticated ultrasound techniques and liberal use of fine-needle aspiration (FNA) biopsies have detected subclinical disease.7,8
Etiologies for incidental thyroid nodules can be divided into benign and malignant causes. Benign etiologies include thyroid cyst (simple or complex), multinodular goiter, and Hashimoto’s thryoiditis, while malignant causes include papillary, medullary, follicular, Hurthle cell, and anaplastic carcinomas, thyroid lymphomas, and rare instances of metastatic cancers.2,3
Targeted history and physical examination helps to characterize the thyroid incidentaloma. Historical features, such as palpitations, weight loss, anxiety, new onset atrial fibrillation, or menstrual irregularities, coupled with tachycardia, tremors, proximal muscle weakness, and a palpable nodule aid in the diagnosis of hyperthyroidism. Findings such as a family history of thyroid cancer, symptoms of hoarseness or dysphagia, rapid growth of the nodule, environmental or history of head or neck irradiation along with physical findings of a hard, fixed nodule, or cervical lymphadenopathy increase the suspicion for malignancy.2,7
The functionality of the nodule can be assessed by checking TSH, free T3, and free T4 levels. Suppression of TSH (< 0.1 mU/L) with elevated levels of free T3 and T4 indicates nodule production of excess thyroid hormone and warrants thyroid scintography. Thyroid scintography will identify the nodule as “hot” (hyperfunctioning) or “cold” (nonfunctioning).2
Regardless of the radiographic modality that initially identified the thyroid incidentaloma, a dedicated thyroid high-resolution ultrasound should be ordered to assess the size, multiplicity (single or multinodular), location, and character (solid, cystic, or mixed).7
Recommendations for proceeding to FNA to evaluate for malignancy differ among subspecialty societies. Generally, nodules larger than 1 cm or nodules smaller than 1 cm with risk factors for malignancy should be referred for FNA.2,7
If diagnostic workup identifies a patient with hyperthyroidism due to an autonomously functional nodule or a nodule that may be at high risk for malignancy, it is appropriate to involve an endocrinologist and possibly a surgical subspecialist prior to discharge. Management of hyperthyroidism can include starting antithyroid agents (methimazole or propylthiouracil), radioactive iodine ablation, or referral for surgery.
Preparation for discharge of the patient whose incidentaloma is nonfunctional or does not appear to be malignant should include appointments to recheck thyroid hormone levels, including TSH as well as a thyroid ultrasound within one year of the initial discovery.
Adrenal incidentaloma. The prevalence of AIs found by CT of the abdomen ranges from 0.4% to 4%, while autopsy studies have found a prevalence of 1.4% to 9% with increasing prevalence with age.2,9,10 The majority of AIs are benign and nonfunctioning adenomas, in the absence of known malignancy. Other differential diagnoses include Cushing’s syndrome, pheochromocytoma, adrenocortical adenoma, aldosteronoma, and metastatic lesions.
Because functioning adrenal incidentalomas may be clinically silent, any patient found with an AI must undergo biochemical workup as part of their evaluation to assess for pheochromocytoma, Cushing’s syndrome, and if he or she has a history of hypertension or hyperaldosteronism (Conn’s syndrome). Table 3 outlines the approach for characterizing adrenal incidentalomas.2,11,12 An important point is that imaging studies are not useful in distinguishing a functioning versus nonfunctioning tumor but rather can help to discriminate malignant lesions.11
Inpatient surgical consult for resection is indicated if the patient is found to have pheochromocytoma, clinically apparent functioning adrenocortical adenoma, or a tumor size greater than 4 cm. Consultation with an endocrinologist is also recommended if biochemical tests are positive. If the diagnostic workup leads to suspicion for infection or metastatic disease, the patient should be referred for FNA.2,12
For patients whose lesions do not require surgical resection, repeat CT scan of the abdomen is recommended six months from the initial finding. Hospitalists should also arrange for the patient to repeat biochemical testing, including an overnight dexamethasone test.12,13
Back to the Case
The patient underwent biochemical testing and was found to have normal levels of plasma-free metanephrines, a plasma aldosterone, plasma renin activity ratio less than 20, and a serum cortisol level of 7 mg/dL after his overnight dexamethasone suppression test. The 24-hour urine collection for free cortisol revealed elevated levels of cortisol in the urine, and the ACTH level was low.
Endocrinology and endocrine surgery teams were consulted, and recommended surgical resection. After surgical resection of his tumor, the patient was started on glucocorticoid replacement and was discharged with a follow-up appointment with endocrinology.
Bottom Line
An inpatient approach to endocrine incidentalomas should include characterization of the clinical signs and symptoms, size, function, and malignant potential of the lesion. Based on this, inpatient surgical or medical management can be determined. Post-discharge management should include arrangements for surveillance testing and follow-up with appropriate subspecialists.
Dr. Tad-y is assistant professor of medicine and a hospitalist at the University of Colorado Denver.
References
- Aron DC, Howlett TA. Pituitary incidentalomas. Endocrinol Metab Clin North Am. 2000;29:205-221.
- Shirodkar M, Jabbour SA. Endocrine incidentalomas. Int J Clin Pract. 2008;62:1423-1431.
- Burguera B, Gharib H. Thyroid incidentalomas. Prevalence, diagnosis, significance, and management.Endocrinol Metab Clin North Am. 2000;29:187-203.
- Molitch ME. Nonfunctioning pituitary tumors and pituitary incidentalomas. Endocrinol Metab Clin North Am. 2008;37:151-171, xi.
- Freda PU, Beckers AM, Katznelson L, et al. Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:894-904.
- Gough J, Scott-Coombes D, Fausto Palazzo F. Thyroid incidentaloma: an evidence-based assessment of management strategy. World J Surg. 2008;32:1264-1268.
- Iyer NG, Shaha AR, Silver CE, et al. Thyroid incidentalomas: to treat or not to treat. Eur Arch Otorhinolaryngol. 2010;267:1019-1026.
- Jin J, Wilhelm SM, McHenry CR. Incidental thyroid nodule: patterns of diagnosis and rate of malignancy. Am J Surg. 2009;197:320-324.
- Davenport C, Liew L, Doherty B, et al. The prevalence of adrenal incidentaloma in routine clinical practice.Endocrine. 2011;40:80-83.
- Zeiger MA, Siegelman SS, Hamrahian AH. Medical and surgical evaluation and treatment of adrenal incidentalomas. J Clin Endocrinol Metab. 2011;96: 2004-2015.
- Zeiger MA, Thompson GB, Duh QY, et al. American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons Medical Guidelines for the Management of Adrenal Incidentalomas: executive summary of recommendations. Endocr Pract. 2009;15:450-453.
- NIH state-of-the-science statement on management of the clinically inapparent adrenal mass (“incidentaloma”).NIH Consens State Sci Statements. 2002;19:1-25.
- Young WF. Clinical practice. The incidentally discovered adrenal mass. N Engl J Med. 2007;356:601-610.
- Chidiac RM, Aron DC. Incidentalomas. A disease of modern technology. Endocrinol Metab Clin North Am. 1997;26:233-253.
