Case Report. Michael H. Goldman, MD; Alison T. Gruber; Marc A. Herman, MD ABSTRACT

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1 Case Report CONCURRENT PANHYPOPITUITARISM AND HYPERPROLACTINEMIA DUE TO A GIANT INTERNAL CAROTID ANEURYSM REVEALED BY THYROID HORMONE WITHDRAWAL DURING FOLLOW-UP MANAGEMENT OF THYROID CANCER Michael H. Goldman, MD; Alison T. Gruber; Marc A. Herman, MD ABSTRACT Submitted for publication April 0, 05 Accepted for publication July, 05 From the Englewood Hospital; Englewood Cliffs, New Jersey. Address correspondence to Dr. Michael H. Goldman, Englewood Hospital, 600 E Palisade Avenue #, Englewood Cliffs, New Jersey mgoldman@verizon.net. DOI:0.458/EP578.CR To purchase reprints of this article, please visit: Copyright 06 AACE. Objective: This article reports a case of secondary hypothyroidism occurring during the withdrawal of thyroid hormone replacement in a patient with thyroid cancer that led to the discovery of simultaneous panhypopituitarism and hyperprolactinemia that were caused by an internal carotid artery aneurysm. The discovery of the secondary hypothyroidism necessitated further pituitary hormone analysis and medical imaging to identify the precise pathologic etiology. Methods: The methods used included the evaluation of selected thyroid and pituitary hormone concentrations and subsequent pituitary magnetic resonance imaging. Results: An 86-year-old African-American female with a history of thyroid cancer exhibited a suppressed serum thyroid-stimulating hormone concentration that failed to increase during progressive lowering of her thyroxine dosage despite it causing a simultaneous subnormal free thyroxine concentration. Laboratory findings indicated secondary hypothyroidism and subsequently panhypopituitarism and hyperprolactinemia. Pituitary magnetic resonance imaging revealed the presence of a large carotid aneurysm that had invaded the sella turcica. Additional hormone analyses revealed elevated prolactin, low gonadotropins, low baseline cortisol within an inappropriately normal adrenocorticotropic hormone concentration, and a low cortisol concentration following cortrosyn stimulation. Conclusion: Panhypopituitarism and hyperprolactinemia were revealed in a patient with thyroid cancer during thyroid hormone withdrawal, leading to the discovery of a giant internal carotid artery aneurysm invading the pituitary fossa. Physicians should be alert to the possibility of secondary hypopituitarism when an expected rise in thyroid-stimulating hormone while tapering thyroid hormone replacement in a low risk thyroid cancer patient fails to occur. (AACE Clinical Case Rep. 06;:e67-e7) Abbreviations: FT4 = free thyroxine; TSH = thyroid stimulating hormone; MRI = magnetic resonance imaging; GICAA = giant internal carotid artery aneurysm INTRODUCTION Treatment of thyroid cancer usually requires thyroid gland ablation followed by thyroid hormone administration to suppress thyroid-stimulating hormone (TSH) concentrations to subnormal levels. If there is no evidence of recurrence during follow-up as shown by low thyroglobulin concentrations, a neck sonogram appears normal, and the patient is in the appropriate low-risk category, reduced exogenous thyroid hormone supplementation is encouraged, especially in the elderly (). We report the case of a patient treated with thyroidectomy and radioactive iodine therapy whose serum TSH remained suppressed despite tapering her free thyroxine (FT4) to a subnormal level. Upon investigation of the secondary hypothyroidism, a carotid aneurysm was unexpectedly found along with multiple pituitary hormone abnormalities. Copyright 06 AACE AACE CLINICAL CASE REPORTS Vol No. Spring 06 e67

2 e68 Sellar Aneurysm With Low TSH, AACE Clinical Case Rep. 06;(No. ) Copyright 06 AACE CASE REPORT An 86-year-old African-American female had been treated for thyroid cancer for 6 years since her initial diagnosis. She previously had a multi-focal follicular variant papillary cancer (T N 0 M 0 ) involving both lobes of her thyroid and underwent a total thyroidectomy and radioactive iodine therapy. She did well postoperatively with a Thyrogen -stimulated thyroglobulin concentration of less than 0. ng/ml and a negative neck ultrasound. Her other medical problems included accelerated hypertension being treated with multiple medications, elevated blood cholesterol for which she was taking Lipitor, chronic renal disease with a creatinine concentration of.0 mg/dl, and breast cancer treated in 007. The patient was clinically well without complaints. Her blood pressure was 30/80 mmhg and her pulse was 7 beats per minute. Her reflexes were normal as was the remainder of her exam. Due to her age and low risk for cancer recurrence as indicated by a thyroglobulin concentration of less than 0. ng/ml (normal range.5 to 38.5 ng/ml) and a negative ultrasound, an attempt was made beginning in September 0 to normalize her suppressed TSH concentration by slowly lowering her dose of exogenous FT4 (Table ). Despite an unusually low medication dose causing her FT4 concentration to be subnormal, her TSH remained inappropriately low at 0.9 miu/l and 0.35 miu/l (normal range 0.4 to 4.5 miu/l ) rather than the expected elevated values. It should be noted that she did have an elevated TSH of 6 U/mL postoperatively in 009. The simultaneously low FT4 and TSH concentrations despite thyroid hormone withdrawal 6 years after thyroidectomy were considered to be indicative of secondary hypothyroidism. A cranial magnetic resonance imaging (MRI) was performed that revealed an expansile sellar/suprasellar mass measuring 3.0 x.7 cm with compression and effacement of the pituitary gland as well as encroachment of the right cavernous sinus that was consistent with a giant internal carotid artery aneurysm (GICAA). In addition, pituitary stalk compression was identified but no tumor was observed (Fig. ). Subsequent evaluations revealed the presence of panhypopituitarism and hyperprolactinemia, with a luteinizing hormone concentration of 0. miu/ml (normal post-menopausal range 0.9 to 58.6 miu/ml), follicle-stimulating hormone 4. miu/ml (normal postmenopausal range 6.7 to 3.6 miu/ml), cortisol.8 mg/dl (normal range 6.7 to.6 mg/dl), and a simultaneous inappropriately normal adrenocorticotropic hormone concentration of pg/ml (normal range 0 to 60 pg/ ml). In addition, a blunted 8 am cortrosyn test revealed a basal cortisol concentration of 4.6 mg/dl, 30 minute cortisol of.6 mg/dl, and 60 minute cortisol of 5.3 mg/ dl. Prolactin was elevated at 85 ng/ml (normal range 4.8 to 3.3 ng/ml). Table Thyroxine Tapering Schedule a Date TSH (miu/l) Free T4 (ng/dl) Thyroxine dosage (mg/day) 5/ to 0.5 7/ No change 7/ / 0.6 No change 9/ / (5x/week) (½ x/week) 6/ / No change 5/ / (4x/week) 0.05 (½ 3x/week) 0.05 (3x/week) 0.05 (½ 4x/week) 7/ No change 7/ No change 8/ /5 0.9 Abbreviations: T4 = thyroxine; TSH = thyroid-stimulating hormone. The normal concentration range for TSH is 0.4 to 4.5 miu/l and for free T4 is 0.8 to.8 ng/dl. a = decrease in concentration;

3 Copyright 06 AACE Sellar Aneurysm With Low TSH, AACE Clinical Case Rep. 06;(No. ) e69 Fig.. Magnetic resonance imaging revealed the presence of a giant internal carotid aneurysm. Table Causes of Decreased Serum Thyroid-stimulating Hormone Decreased serum thyroid-stimulating hormone associated with subclinical hyperthyroidism Grave s disease Autonomous adenoma Multinodular goiter Thyroiditis Excessive administration of thyroid hormone Decreased thyroid-stimulating hormone not associated with subclinical hyperthyroidism Nonthyroidal illness Acute psychiatric disease Pituitary and hypothalamic disorders Pregnancy Medications (dopamine, glucocorticoids, aspirin, fenlofenac, furosemide) Advanced age

4 e70 Sellar Aneurysm With Low TSH, AACE Clinical Case Rep. 06;(No. ) Copyright 06 AACE DISCUSSION After several years of thyroid replacement therapy, low-risk thyroid cancer patients may pursue FT4 titration to a more physiologic state to reverse TSH suppression and return it back into the normal range. The failure to rebound in our patient led to the discovery of secondary hypothyroidism. Although other causes of low TSH were considered, including her advanced age and multiple medical problems, these potential causes seemed unlikely since her TSH was elevated just a few years earlier (Table ) (). It should be noted that unlike long-standing hypothyroidism where symptoms of fatigue, weight gain, dry skin, and constipation are common, this patient showed no apparent adverse consequences of her low thyroid level since its correction into the normal range was made within a 4 to 6 week period (Table ). Ultimately, pituitary MRI revealed the presence of a GICAA with thrombus. Although a magnetic resonance angiogram of the pituitary could have aided in the confirmation of the aneurysm, the patient requested no further imaging studies. The thrombus seen on the current MRI was consistent with the diagnosis. Other imaging studies, including contrast-enhanced computed tomography, showed an intense homogeneous blush suggesting an aneurysm. Angiography had been used previously to make this diagnosis; however, it is substantially more invasive and has been mostly replaced by MRI/ magnetic resonance angiography (3). Angiography is often utilized prior to planned neurosurgery. Vascular tumors of the pituitary are rare. In large study, aneurysms represented only of 83 documented cases of non-pituitary masses of the sellar (Table 3) (4). MRI has been best shown to differentiate between various disease etiologies (5). Previously, GICAA was found to be associated with both hypopituitarism and hyperprolactinemia (6). In fact, a prolactin concentration of,403 ng/ml has been documented in GICAA without concurrent pituitary tumor (7). Presumably, prolactin was elevated secondary to pituitary stalk compression. It has been previously reported that both the panhypopituitarism and the hyperprolactinemia can be completely resolved by resection of the mass lesion (6). Concurrent pituitary macroadenomas have also been reported to coexist with GICAA (8). Because the patient remained normotensive and was without orthostatic changes, no basal cortisol supplement was advised. Due to the subnormal cortisol response to stimulation, administration of additional steroid hormone was advised during periods of stress. At a thyroxine dose of 0.05 µg/day, the FT4 concentration remains in the normal range and TSH is no longer used for titration because of the Table 3 Diagnoses in 83 Patients with Non-Pituitary Sellar Masses Diagnosis Patients (n) % Cysts Rathke s cleft cyst Epidermoid cyst Arachnoid cyst Other cyst types Parasellar lesions Craniopharyngioma Chordoma Meningioma Lymphoma Mucocele Metastatic carcinoma Breast Prostate Lung Renal cell Parotid Sinonasal undifferentiated carcinoma Unknown Primary Granulomatous and infectious Sarcoid Granulomatous hypophysitis Lymphocytic hypophysitis 5 6 Aneurysm

5 Copyright 06 AACE Sellar Aneurysm With Low TSH, AACE Clinical Case Rep. 06;(No. ) e7 possibility of panhypopituitarism (9). The patient refused further neurosurgical consultation and remains clinically well on her current dosage of thyroid hormone nearly year after her initial diagnosis. Coexistent low FT4 and TSH levels indicate the need for further pituitary testing and imaging studies. CONCLUSION In summary, the presence of a low thyroxine concentration in conjunction with a low TSH concentration led to the discovery of an unexpected GICAA invading the pituitary fossa, the cause of this patient s secondary hypothyroidism, and ultimately produced a diagnosis of panhypopituitarism and hyperprolactinemia. DISCLOSURE The authors have no multiplicity of interest to disclose. REFERENCES. Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 009;6: Surks MI, Ocampo E. Subclinical thyroid disease. Am J Med. 996;00: Powell DF, Baker HL Jr, Laws ER Jr. The primary angiographic findings in pituitary adenomas. Radiology. 974;0: Freda PU, Wardlaw SL, Post KD. Unusual causes of sellar/parasellar masses in a large transsphenoidal surgical series. J Clin Endrocinol Metab. 996;8: Rennert J, Doerfler A. Imaging of sellar and parasellar lesions. Clin Neurol Neurosurg. 007;09: Verbalis JG, Nelson PB, Robinson AG. Reversible panhypopituitarism caused by a suprasellar aneurysm: the contribution of mass effect to pituitary dysfunction. Neurosurgery. 98;0: Duarte FH, Machado MC, Lima JR, Salgado LR. Severe hyperprolactinemia associated with internal carotid artery aneurysm: differential diagnosis between prolactinoma and hypothalamic-pituitary disconnection. Arq Bras Endocrinol Metab. 008;5: Wang CS, Yeh TC, Wu TC, Yeh CH. Pituitary macroadenoma coexistent with surpraclinoid internal carotid artery cerebral aneurysm: a case report and review of the literature. Cases J. 009;: Persani L, Bonomi M. Uncertainties in endocrine substitution therapy for central endocrine insufficiencies: hypothyroidism. Handbook of Clinical Neurology. 04;4: