Panhypopituitarism

Clinical panhypopituitarism caused by cancer with parasellar metastasis and hypothalamic invasion is very rare. This report concerns a lung cancer patient who had solitary parasellar metastasis with diabetes insipidus and panhypopituitarism as an initial manifestation, which was documented by contrast-enhanced computed tomographic scan, Gd-DTPA-enhanced magnetic resonance imaging, and endocrinologic studies.

Lung cancer is the leading cause of cancer death of both men and women in developed countries and has a variety of clinical manifestations. Panhypopituitarism is an unusual initial clinical presentation of metastatic disease from lung cancer. Reported incidence of pituitary metastases is 1 percent to 6 percent.[1-3] Breast and lung cancers are most frequent sites in women and in men, associated with pituitary metastases.[4] Metastases to the hypothalamus are much less frequent than to the pituitary gland.[4] Diabetes insipidus secondary to cancer metastases is the most frequent manifestation of endocrine deficiency for pituitary-hypothalamic metastases,[4] and anterior pituitary failure occurs much more infrequently. This report describes a female patient who had lung cancer with solitary parasellar metastasis that had presented initially as transient diabetes insipidus and panhypopituitarism.

CASE REPORT

A 67-year-old woman previously in good health was admitted to the hospital with general malaise, apathy, nausea, vomiting, and polydipsia of 2 months' duration. She had no history of smoking or alcohol abuse. At the time of hospital admission, she was obtunded and in no acute distress. Her blood pressure was 90/50 mm Hg with a regular heart rate of 98 beats/min. On cardiovascular examination, there was no jugular venous distention or audible gallops. She had no respiratory symptoms of cough, expectoration, hemoptysis or dyspnea, and chest examination revealed no wheezing or crackles. Abdominal examination revealed no hepatosplenomegaly and local tenderness, and no mass could be palpated. The eye ground examination showed no papilledema, and visual field examination showed mild asymmetric bitemporal visual defect. The remainder of the physical examination, including the nervous and reproductive systems, shoed no abnormality. The relevant laboratory data were as follows: serum sodium, 161 mEq/L; potassium, 3.9 mEq/L; chloride, 120 mEq/L; and serum osmolarity, 294 mosm/kg; the urine amount was 3,9000 ml daily and urine sodium was 10 mEq/L, potassium was 7 mEq/L, chloride was 15 mEq/L, and osmolarity was 102 mosm/kg. The complete blood cell count and biochemistry analysis results were normal.

Initial evaluation with chest radiograph and computed tomograms (CT) (Fig 1) revealed an ill-defined mass near the right hilar area: the chest sonography also demonstrated an isoechoic mass; the cytologic results of sputum and ultrasound-guided perentaneous aspiration all revealed adenocarcinoma. ACT scan and contrast-enhanced magnetic resonance image (MRI) were done to evaluate the sella turnica because panhypopituitarism with diabetes insipidus was suspected. An ill-defined mass that extended from the dorsum sellae to the pituitary fossae anteriorly and hypothalamus superiorly was found (Figs 2 and 3). Other staging work-up, including bone scan and CT scan of the abdomen, did not disclose other metastatic lesions.

Hypothalamic and pituitary function tests were performed and are summarized in Table 1. The baseline serum levels of cortisol. thyrotropin, triiodothyronine, thyroxine, growth hormone, and corticotropin were abnormally low. The serum prolactin level was highly elevated. After pituitary stimulation with corticotropin-releasing hormone, thyrotropin-releasing hormone, growth hormone-releasing hormone, and luteinizing hormone-releasing hormone, serum levels of corticotropin, cortisol, thyrotropin, growth hormone, follicle-stimulating hormone, and luteinizing hormone levels were all elevated. but peak hypophyseal hormone responses were delayed. Secondary panhypopituitarism and diabetes insipidus due to hypothalamic dysfunction, which was the result of cancer metastasis, were considered; then oral levothyroxine, 0.05 mg daily, was given as supplement therapy. Prednisolone, 30 mg daily, was given for adrenal insufficiency and possible increased intracranial pressure. The polyuria from diabetes insipidus was controlled by desmopressin (DDAVP) successfully. The sella turcica area was irradiated with 3,000 cGy of cobalt-60 over a 15-fraction period. Symptoms of nausea, vomiting, general malaise, and polyuria improved after treatments. The patient survives more than 4 months after diagnosis without any symptom up until the present time, and is under regular follow-up at the outpatient department.

DISCUSSION

Endocrinologic abnormalities are common paraneo-plastic syndromes seen in lung cancer. Most of the endocrinologic abnormalities associated with lung cancer result from excessive secretion of hormones or hormone-like substance, such as syndrome of inappropriate secretion of antidiuretic hormone and Cushing's syndrome.[5-7]

Panhypopituitarism caused by parasellar metastasis is an unusual initial clinical presentation of lung cancer. Hypothalamohypophyseal metastases occur in only 1.8 percent to 6 percent of autopsied cancer cases;[1-3] the metastases to the pituitary gland have been reported much more frequently than metastases to the hypothalamus.[8] Breast carcinoma is the most common malignancy to metastasize to the pituitary gland in women. Lung and prostate carcinoma are the most common tumors with pituitary metastasis in men.[4] These metastatic lesions involve the neurohypophysis about twice as frequently as the adenohypophysis,[8] and cause a 6.8 percent incidence of diabetes insipidus.[4,8,9]

Previously, anterior pituitary insufficiency was reported to occur in only 2 percent of metastatic cancer cases.[3] Few of these presented with clinical adenohypophyseal deficiency.[10-12] Branch and Laws[13] recently reported a 64 percent incidence of panhypopituitarism in cases of pituitary metastases.

Panhypopituitarism from metastases is most often the result of hypothalamic rather than adenohypophyseal invasion,[8,14,15] which occurred in this case. Metastatic lesions rarely localize in the adenohypophysis because it does not receive a direct systemic blood supply, and anterior pituitary involvement is usually the result of direct invasion from the posterior lobe.[1,8,16] Although an intact adenohypophysis and extensive infundibular invasion would be expected to cause hyperprolactinemia due to blockage of hypothalamus-derived prolactin-inhibiting factor in our case, the same conditions were documented only twice before.[11,13]

[TABULAR DATA OMITTED]

In this case, tertiary hypoadrenalism and hypothyroidism with diabetes insipidus were considered, and correlated with the findings in brain CT and MRI, which had revealed a hypothalamic infundibular tumor with invasion to the posterior lobe of the pituitary gland. Although there was no histologic diagnosis of the parasellar tumor, according to the clinical presentations and endocrinologic, radiologic evaluations, lung cancer with parasellar metastases and hypothalamic, posterior pituitary invasion was the most probable diagnosis for this case.

A CT scan cannot reliably distinguish metastases from pituitary adenoma;[10,17] however, MRI with intravenous Gd-DTPA is more sensitive in detecting and defining the extent of abnormality in brain-stem tumor.[18] Magnetic resonance imaging with sagittal and coronal sections can identify most clearly small pituitary tumors, and has proved effective in demonstrating the hypophyseal stalk, optic chiasm, and anterior third-ventricle anatomy.[19] However, it was still difficult to differentiate between metastasis to hypothalamus and extension into sella via neurohypophysis or vice versa by MRI study.

Using contrast-enhanced MRI and with the help of endocrinologic evaluations, metastatic parasellar tumor can be differentiated from the primary pituitary tumor and can prevent underestimating the incidence of hypothalamopituitary dysfunction, the initial presentations of malignancies. Thus, appropriate treatment such as cranial radiation need not be delayed.

REFERENCES

[1] Kovacs K. Metastatic cancer of the pituitary gland. Oncology 1973; 3:533-42

[2] Max MB, Deck MDF, Rottenberg DA. Pituitary metastasis: incidence in cancer patients and clinical differentiation from pituitary adenoma. Neurology 1981; 8:998-1002

[3] Nugent JL, Bunn PA, Matthews MJ, Ihde DC, Cohen MH, Gazdar A, et al. CNS metastases in small cell bronchogenic carcinoma. Cancer 1979; 44:1885-93

[4] Teears RJ, Silverman EM. Clinicopathologic review of 88 cases of carcinoma metastasis to the pituitary gland. Cancer 1975; 36:216-20

[5] Maurer LH. Ectopic hormone syndromes in small cell carcinoma of the lung. Clin Oncol 1985; 4:67-83

[6] List AF, Hainsworth JD, Davis BW, Hande KR, Greco FA, Johnson DH. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in small cell lung cancer. J Clin Oncol 1986; 4:1191-98

[7] Gewirtz G, Yalow RS. Ectopic ACTH production in carcinoma of the lung. J Clin Invest 1974; 53:1022-32

[8] Modhi G, Bauman W, Nicolis G. Adrenal failure associated with hypothalamic and adrenal metastases. Cancer 1981; 47:2098-101

[9] Noseda A, Louis O, Mockel J, Yernault JC. Case report: diabetes insipidus from metastatic oat cell carcinoma: recovery after brain irradiation. Am J Med Sci 1985; 289:27-30

[10] Buonaguidi R, Ferdeghini M, Faggionato F, Tusini G. Intrasellar metastasis mimicking a pituitary adenoma. Surg Neurol 1983; 20:373-78

[11] Leramo OB, Booth JD, Zinman B, Bergeron C, Sima AAF, Morley TP. Hyperprolactinemia, hypopituitarism, and chiasmal compression due to carcinoma metastatic to the pituitary. Neurosurgery 1981; 8:477-80

[12] Epstein S, Ranchol M, Goldswain PRT. Pituitary insufficiency, inappropriate antidiuretic hormone (ADH) secretion, and carcinoma of the bronchus. Cancer 1973; 32:476-81

[13] Branch CL, Laws ER. Metastatic tumors of the sella turcica masquerading as primary pituitary tumors. J Clin Endocrinol Metab 1987; 65:469-74

[14] Elsie MA, Shantha RK, Archie P. Infundibular metastasis and panhypopituitarism. J Nat Med Assoc 1988; 81:325-30

[15] Duchen LW. Metastatic carcinoma in the pituitary gland and hypothalamus. J Pathol Bacteriol 1966; 91:347-55

[16] Houck WA, Olson KB, Horton J. Clinical feature of tumor metastasis to the pituitary. Cancer 1970; 26:656-59

[17] Max MB, Deck MDF, Rottenberg DA. Pituitary metastasis: incidence in cancer patients and clinical differentiation from pituitary adenoma. Neurology 1981; 31:998-1002

[18] Peterman SB, Steiner RE, Bydder GM, Thomas DJ, Tobias JS, Young IR. Nuclear magnetic resonance imaging (NMR), (MRI), of brain stem tumors. Neuroradiology 1985; 27:202-07

[19] Robert O, Paul FJN, Ferdinando SB, Ian LP, Philip K, Robert D, et al. MR imaging of pituitary adenoma using a prototype resistive magnet: preliminary assessment. AJNR 1984; 5:131-37

COPYRIGHT 1994 American College of Chest Physicians
COPYRIGHT 2004 Gale Group