• with an FSH- and TSH-secreting

JOHN BERMINGHAM, DO LOUIS C. HAENEL, DO

A 34-year-old man was found noma is rare. The combined secretion of follicle- to have elevated thyroxine (T 4 ), triiodothy- stimulating hormone (FSH) and TSH by a pi- ronine (T3 ), calculated free T4 , - tuitary adenoma is rarer. But with current stimulating hormone (TSH), follicle-stimu- widespread use of TSH assays, plus the future lating hormone (FSH), and alpha subunits clinical availability of more sensitive TSH as- of TSH and FSH. A computed tomography says as well as TSH bioactivity testing, more scan of the head showed a 16-mm mac- patients will have pituitary-induced hyperthy- roadenoma of the . There roidism correctly diagnosed, and the disorder was no evidence of loss or excess secre- will be better understood. tion of other pituitary hormones. The large As illustrated in the following case study, chromophobe adenoma was removed via making the correct diagnosis of primary ver- a transphenoidal approach. The patient sus secondary hyperthyroidism is imperative has been taken off all medication. Thyroid because the treatment and potential conse- function has returned to normal and there quences of each of these diseases are totally has been no loss of pituitary secretory ca- different. pacity of other pituitary hormones. The oc- currence of a combined TSH- and FSH- Report of case secreting pituitary adenoma is rare; to the In August 1985, a 34-year-old man was seen with authors knowledge, only one case has complaints that were initially vague and nonspe- been documented in the literature. cific. On thorough questioning, however, he re- ported periods of excessive sweating, some degree of heat intolerance, mild insomnia, tremulousness, Hyperthyroidism caused by thyroid-stimu- dizziness, palpitations, emotional lability, anxiety, lating hormone (TSH )—secreting pituitary ade- and compulsive eating that had led to weight gain. The patient had no sexual dysfunction or loss of libido. From the department of endocrinology and metabolism, The patient, the father of two children, had a University of Medicine and Dentistry of New Jersey— benign medical history. He had had "infectious hepa- School of Osteopathic Medicine. titis" a few years previously. His father had "some kind of thyroid disorder 40 years ago," specifics of Dr Bermingham is chief pulmonary fellow; Dr Haenel which were unobtainable. is head, department of endocrinology and metabolism. Physical examination revealed an enlarged thy- Reprint requests to John Bermingham, DO, John F. roid gland, approximately 1.5 times normal size, Kennedy Memorial Hospital, University Medical Cen- slightly more full on the right side. No adventi- ter, Laurel Rd, Stratford, NJ 08084. tious sounds were heard over the gland or the chest

1560 • JAOA • Vol 89 • No 12 • December 1989 Case report • Bermingham and Haenel wall. The extraocular muscles were intact. Find- mal, 30%-40%); calculated free T4, 7.5 units (refer- ings of funduscopic examination were normal. An ence laboratory normal, 1.5-5.2 units); and TSH at eye examination revealed no detectable thyroid- 8.81.A.U/mL (reference laboratory normal, 0-7 RU/mL). related abnormalities. No dermopathy, tremors, A computed tomography (CT) scan of the head muscle weakness, or onycholysis could be found. showed a 16-mm pituitary macroadenoma. Arte- Penis and testes were of normal size. Male pattern rial digital subtraction angiography ruled out the hair distribution was normal. There was no gyne- possibility of a carotid artery aneurysm. Results comastia. of formal visual field testing were normal. Pitui- The patient underwent routine screening tests tary integrity of the secretory capacity for other including an electrocardiogram, a complete blood pituitary hormones was evaluated by use of a thy- cell count with differential, and a biochemistry pro- rotropin-releasing hormone (TRH )–stimulation file. All results were within normal limits. The se- testi-2 (Table 1); an insulin tolerance testa (Table rum thyroxine (T4) concentration by radioimmu- 2); and measurements of fasting TSH, FSH, leuti- noassay (RIA) was elevated to 16.3 Rg/dL (refer- nizing hormone (LH), and the alpha subunits of ence laboratory normal, 4.5-12.5 ti,g/dL). Thyroid TSH, LH, and FSH (Table 3). An elevation of FSH function tests performed again 14 days later at 23.6 mIU/mL (reference laboratory normal for showed elevated serum triiodothyronine (T3) by an adult male, 0-20 mIU/mL) and alpha subunit RIA at 316 ng/dL (reference laboratory normal, of FSH at 25p.U/mL (reference laboratory normal, 4.50-12.5 ng/dL). The TSH level was not measured. 7-20 RU/rnL) was noted. The 24-hour thyroid uptake, using 105 of io- No water deprivation test was done to evaluate dine 123, was elevated at 63%. A thyroid scan re- vasopressin release, and no tests were done to meas- vealed a diffusely enlarged, symmetrically involved ure serum testosterone or LH-releasing hormone thyroid gland with no evidence of space-occupying stimulation, or sperm count. disease within the thyroid and no evidence of sub- Surgery was scheduled and the patient was sternal extension of functional tissue. A long-act- treated preoperatively with a 6-week course of pro- ing thyroid stimulator test (LATS) was not done. pranolol hydrochloride (20 mg orally tid) for high The data obtained to this point could be consis- blood pressure and PTU (100 mg orally tid). In Sep- tent with Graves disease. Because the patient was tember 1986, a transphenoidal a young man with a relatively small thyroid gland was performed and a large macroadonoma was re- and the thyrotoxicity appeared to be relatively moved. Routine microscopic examination revealed mild, we decided to start him on propylthiouracil the mass to be a chromophobe adenoma. The ade- (PTU) therapy (100 mg orally three times a day). noma was not examined by electron microscopy or After 3 months of therapy, the patient appeared immunohistochemical staining of tissue. to be significantly improved. His weight was sta- Forty-eight hours following surgery, central dia- ble, and the thyroid gland was barely palpable. Re- betes insipidus developed and the patient was peat had fallen to normal treated with desmopressin acetate (DDAVP). The levels: 13 resin uptake (T3RU), 33% (reference labo- desmopressin therapy led to iatrogenic syndrome ratory normal, 23%-34%); T4 (RIA), 11.5 il.g/dL (ref- of inappropriate secretion of antidiuretic hormone, erence laboratory normal, 4.5-12.5 lig/dL), and cal- and it was discontinued without further sequelae. culated free T4, 3.84 units (reference laboratory nor- Initially, the patient was placed on hydrocortisone mal, 1.1-4.4 units). supplementation. One week after surgery, the pa- The PTU therapy was discontinued after 6 tient was taken off all medication. Laboratory stud- months, at which time thyroid function tests ies at that time indicated normal levels of serum showed T3RU at 40% (reference laboratory normal, electrolytes; urine specific gravity, 1.013; TSH 23%-34%); calculated free T4 at 5.58 units (refer- (RIA), 3.3 mIU/mL (reference laboratory normal, ence laboratory normal, 1.0-4.3 units); T 4 (RIA) at 0-4.9 mIU/mL), and T4 (RIA) 9.7 p.,g/dL (reference 13.8 1.1.g/dL (reference laboratory normal, 4.5-12.5 laboratory normal, 4.5-12.5 Rg/dL). lig/dL); and elevated TSH, 11.1 mIU/mL (reference Currently, the patient has no complaints, and laboratory normal, 0-4.9 mIU/mL). A week later, blood pressure has returned to normal levels. The the same tests were done at an independent labo- patient will be followed up at 6-month intervals ratory indicating and confirming increased values: with thyroid function testing and measurement of T4 (RIA), 18.7 I.Lg/dL (reference laboratory normal, fasting FSH levels. The patient has been advised 5-13 ii,g/dL); T3RU, 40% (reference laboratory nor- that the macroadenoma could recur4 and that an-

Case report • Bermingham and Haenel JAOA • Vol 89 • No 12 • December 1989 • 1561 Table 1 Table 2 Patients Thyroid-Releasing Hormone Patients Insulin Tolerance Test Results (TRH) – Stimulation Test Results Cortisol, Human growth Prolactin, Internal p.g/dL hormone, ng/mLt Internal TSH, mIU/L mIU/Lt Fasting (7 Am) 18.5 1.3 Fasting (7 AM) 6.6 19 Humulin R insulin TRHI: administered intravenously, 0.02 U/kg (more if 500 lig (9:30 Am) needed) administered At 30 minutes (10 Am) 8.2 36 intravenously 36 At 60 minutes (10:30 Am) 8.5 Postinsulin serum glucose nadir 32mg/dL TSH = thyroid-stimulating hormone; reference laboratory normal, 0.00 to 4.90 mIU/L. Results§ Reference laboratory normal range for an adult male, up to 25 mIU/ At 15 minutes (9:45 Am) 27.1 6.6 L. At 30 minutes (10 Am) 27.7 5.9 TRH stimulates TSH and prolactin secretion from the pituitary At 45 minutes (10:15 AM) 29.1 5.1 gland. At 60 minutes (10:30 AM) 28.5 5.3 At 75 minutes (10:45 Am) 24.0 5.2 At 90 minutes (11 Am) 22.0 5.2

*Laboratory reference normal, 7 to 25 pg/c1L at 8 Am; 2 to 9 ug/dL at 4 PM. tLaboratory reference normal, 5 ng/mL. Hypothalamic regulation of other course of therapy or alternate therapy will human growth hormone l hGH I secretion can be altered by drugs that affect catecholamine neurotransmitters. For example, 13-adrenergic blockade be discussed at that time. (propranolol) can facilitate hGH secretion in response to hypoglycemia. /Patient's blood glucose nadir was 32 mg/dL, obtained 25 minutes after injection of insulin. Nadir results should be < 40 mg/dL or 50'a of baseline Discussion level. §Cortisol and human growth hormone were drawn at 15-minute intervals Secondary hyperthyroidism for a total of 90 minutes after glucose nadir. Hyperthyroidism in most cases can be attrib- uted to one of four causes: (1) Graves disease (diffuse toxic goiter); (2) Plummers disease (toxic multinodular goiter); (3) toxic uninodu- lease similar thyrotropins. 78 Other neoplasms, lar goiter (autonomous or "hot" nodules), 5 and including thyroid carcinomas and bronchial car- (4) thyroiditis. cinoma, 19 have displayed thyrotropin-like sub- In the majority of patients with hyperthyroid- stances in the serum or tumor tissue but have ism due to one of these conditions, the serum not yet been implicated as a cause of clinically TSH levels are either extremely low or are apparent or laboratory-documented hyperthy- undetectable by current clinically available roidism. All of the foregoing thyrotropin-like means. This is caused by the negative feed- substances are not detectable by human TSH back which the high T3 and T4 levels exert on (RIA) studies, but may require bioassays9,11 or the hypothalamic and pituitary glands. cross-reaction with antibovine or antiporcine Excessive and autonomous secretion of FSH TSH serum.12 by the pituitary gland, or pituitary adenomas, Increased pituitary thyrotropin production and the production and release of thyrotropin- has occurred by means of a variety of etiolo- like substances by nonpituitary neoplasms gies. Thyroid-stimulating hormone hypersecre- have been reported. Not all of these disorders tion may be caused by partial or total resis- have led to clinically apparent or laboratory- tance of thyrotropes to inhibition by thyroid documented hyperthyroidism. In women, two hormone. 13 Increased TSH secondary to hyper- placental thyrotropins have been isolated— secretion of TRH can lead to tertiary hyper- human chorionic, or placental, thyrotropin and thyroidism. In addition, the presence of a TSH- human chorionic gonadotropin6. These thyro- secreting pituitary adenoma can lead to in- tropins can be secreted in the presence of hy- creased TSH. Because treatment differs depend- datidiform moles and choriocarcinomas. In ing on the cause of hyperthyroidism, identifi- men, primary or metastatic embryonal carci- cation of these other causes is clinically sig- noma or choriocarcinoma of the testes can re- nificant.

1562 • JAOA • Vol 89 • No 12 • December 1989 Case report • Bermingham and Haenel The association of hyperthyroidism and pi- Table 3 tuitary tumors is not new to the medical lit- Measurements of Patients Alpha Subunits of Follicle- erature. Numerous articles and case studies Stimulating Hormone (FSH), Leutinizing Hormone have described and questioned the simultane- (LH), and Thyroid-Stimulating Hormone (TSH) ous occurrence of acromegaly, increased TSH- Hormone and Measurement, Reference laboratory like activity, and hyperthyroidism. 14,16 Many alpha subunit Measurement normal range of these studies were reported prior to the avail- Fasting FSH, mlU/mL 23.6 0-20 ability of precise studies of thyroid and pitui- Fasting LH, mIU/mL 17.0 up to 25 Alpha subunits, p.0/mL tary function. In addition, treatment of thyro- FSH 25 7-20 toxicosis by radiation therapy or surgery di- LH 10 6-17 rected toward the pituitary glanc1 16—and, there- TSH 6 <6 fore, indirectly affecting the hypothalamus— Adult male. has been reported, making speculative a di- rect causal relationship between the pituitary gland and the hyperthyroidism. The mere occurrence of hyperthyroidism in a patient with a pituitary tumor does not mean that the tumor is secreting TSH. It would seem say, and 2 by a nonspecified method. Since that more likely that such a patient has two sepa- time, additional cases have been reported. 8-25 rate entities and may be found to have ele- Patients with TSH-secreting pituitary tu- vated LATS levels or an autonomously func- mors usually have macroadenomas ( > 10 mm tioning thyroid nodule. To prove definitively in diameter) that are locally aggressive and the causal relationship of hyperthyroidism to large enough to cause erosion into the sella a TSH-secreting pituitary adenoma, one must turcica and to cause visual field changes. The base the confirmation on clinical, radioimmu- tumors are usually composed of thyrothrophs nologic, histologic, and immunocytochemical but may contain two different cell types or evidence. stain positive for other trophic hormones. Most In addition to demonstrating a pituitary ade- patients do not have extrathyroidal manifes- noma, either a microadenoma17 or macroade- tations of Graves disease, but there have been noma, one must be able to demonstrate nor- a few cases associated with proptosis, one due mal or elevated levels of TSH (RIA) in con- to direct invasion of the tumor into the orbit.24 junction with elevated T3 (RIA) or T4 (RIA) Not only are TSH (RIA) levels elevated or nor- or both. Microscopic examination should be per- mal in the presence of elevated T3 or T4 or formed and, where available, electron micro- both, but the alpha subunit of TSH (aTSH) has sopy and immunohistochemistry tests should also been found to be elevated in patients with be done to demonstrate the presence of thyro- TSH-secreting pituitary adenomas.26 trophs and TSH (RIA) in the pituitary tumor. A more consistent and discriminatory Treatment directed toward the pituitary tu- method of helping to distinguish thyrotroph mor—surgery, radiation therapy, or drug ther- adenomas from nonadenomatous inappropri- apy—should lead to remission of the hyperthy- ate secretion of TSH is the alpha subunit- roidism. Fulfillment of the foregoing criteria TSH molar ratio. A ratio greater than 1.0 is in all patients with pituitary adenoma is diffi- more consistent with the presence of a thyro- cult, if not impossible. troph adenoma and a ratio less than 1.0 with In 1978, Cooper and associates 5 reviewed nonadenomatous inappropriate TSH secre- the literature and found 19 cases of hyperthy- tion.27 roidism in the presence of normal or elevated TSH-secreting pituitary tumors appear to TSH levels. Fourteen of these patients had pi- function autonomously. The tumors usually ex- tuitary tumors. Nine of the 14 had increased hibit altered response to both positive and nega- TSH levels documented by RIA, 3 by bioas- tive feedback, showing loss of TSH suppressi-

Case report • Bermingham and Haenel JAOA • Vol 89 • No 12 • December 1989 • 1563 bility by dopamine,23 thyroid hormone, and so- rally occurring inhibitors of TSH have lead to matostatin,28 and no response to TRH stimu- elevated T3, T4 response." Pure alpha subunit- lation. In some cases, the TSH secretion is not secreting tumors31 and thyrotroph adenomas32 completely autonomous, as indicated by a vari- have been found in patients with normal TSH, able suppressibility with large doses of thy- T3, and T4 levels and with TSH-secreting mi- roid hormone and only a blunted response to croadenomas. TRH stimulation. 5 TSH may be suppressed by Treatment of the TSH-secreting pituitary tu- glucocorticoid administration, but the alpha mor may not be as straightforward as it first subunit continues to be secreted in excess appears. In the case reported here, as in many amounts. other instances, the patient had already been In the case presented here, the TSH level placed on antithyroid therapy prior to the dis- did increase with TRH administration, but it covery of the pituitary tumor. Some investi- was a blunted response. Since the patient al- gators33 contend that pituitary hyperplasia or ready had signs and symptoms of hyperthy- adenoma transformation may be caused by roidism, it was considered medically unsafe to chronic hypothyroidism leading to pituitary initiate a T3-suppression test for fear of exac- overstimulation. If this is true, treating hy- erbation of the hyperthyroidism. The patient perthyroidism in patients with elevated TSH did not undergo TSH-suppression challenges levels with antithyroid therapy, ablative thy- with administration of dopamine, somatosta- roid surgery, or radiation therapy may lead tin, or glucocorticoid because the results would to unfortunate results. It could lead to hyper- not have changed his clinical course. plasia or possible adenomatous transformation It is not entirely clear when the workup for of a nontumorous gland or growth of a current an underlying TSH-secreting pituitary tumor microadenoma or macroadenoma to the point should be initiated in patients with hyperthy- of causing sellar or parasellar compressive roidism. Certainly, hyperthyroid patients with symptoms. To treat the tumor with T 3-suppres- known elevated TSH levels and patients with sive therapy would most likely worsen the thy- sellar or parasellar pressure symptoms, such rotoxicosis. as visual field loss or evidence of loss of pitui- There have been some trials using bro- tary hormones, should be evaluated immedi- mocriptine19,29 and 3, 5, 3-triiodothyroacetic ately for the possibility of pituitary tumor. To acid therapy. 21 Neither is currently approved measure TSH levels routinely as part of the for clinical use for this condition. The best treat- initial workup of a clinically hyperthyroid pa- ment available at present is surgical removal tient is not cost-effective. But, as in the case of the tumor or radiation therapy. If, for any reported here, if the patient lacks clinical evi- reason, the patient is unable to undergo sur- dence of Graves disease or autoimmune dia- gery or radiation therapy, or if these treatment thesis, or if the patient fails adequate thyroid modalities fail to decrease T3, T4, and TSH lev- ablative therapy, then an evaluation of the els after several attempts, therapy should be TSH level along with an evaluation of the se- directed to the thyroid gland. As with all dis- rum thyroid hormone levels may be beneficial. eases, more precise and accurate therapy will If the TSH level is found to be suppressed be devised once the cause of the tumor has in the presence of elevated T3/T4 levels, this been clarified. fact does not exclude TSH as a cause of the hyperthyroidism. Not only do newer, more sen- FSH-secreting pituitary tumor sitive tests show the persistent elevation of A pituitary tumor secreting both FSH and TSH levels in patients grossly hyperthyroid, TSH is extremely rare. Only one case has been but studies have shown variable biologic ac- reported in the literature to date. Our patient tivity of TSH29 with either lower biologic ac- had a macroadenoma of the pituitary with ele- tivity25 or increased biologic activity. 22 In ad- vated FSH, aFSH, and TSH, aTSH, T3, and dition, it has been shown that the loss of natu- T4. There was no evidence of gonadal dysfunc-

1564 • JAOA • Vol 89 • No 12 • December 1989 Case report • Bermingham and Haenel tion. The patient had a normal adult male pe- tinue to evaluate clinical indicators and nis and normal testes, normal male hair dis- subunit levels along with pituitary function tribution, and no gynecomastia, and he had tests to help in screening for patients with a fathered two children. Laboratory studies that TSH-secreting pituitary tumor. were not done included measurement of serum testosterone levels, sperm count, and luteiniz- ing hormone-releasing (LHRH) determination 1. either before or after surgery. A testicular bi- Snyder PJ, Utiger RD: Response to thyrotropin releasing hor- mone (TRH) in normal man. J Clin Endocrinol Metab opsy was not performed. 1972;34:380. Gonadotropin-secreting pituitary adenomas 2. Hall R, Besser GM, Ormston BJ, et al: The thyrotropin re- occurring alone are also fairly rare. leasing hormone test in diseases of the pituitary and hypotha- 34-36 When lamous. Lancet 1972;1:7754-7763. such tumors do appear, they are usually mac- 3. Rosenfeld PS, Wool MS, Dainforth E Jr: Growth hormone roadenomas and usually occur in men with response to insulin-induced hypoglycemia in thyrotoxicosis. J prior hypogonadism. It is believed that these Clin Endocrinol 1969;29:777-780. 4. ODonnell J, tumors arise due to loss of negative feedback Hadden DR, Werner JA, et al: Thyrotoxicosis recurring after surgical removal of a thyrotropin-secreting pi- leading to pituitary overstimulation, hyperpla- tuitary tumor. Proc R Soc Med 1973;66:441-442. sia, and adenomatous transformation. The pa- 5. Cooper DS, Ridgway EC, Maloof F: Unusual types of hyper- tient with a tumor may have elevated FSH thyroidism. Clin Endocrinol Metab 1978;7(1):199-220. 6. levels alone or in combination with elevated Kenimer JG, Heasbman JM, Higgins HP: The thyrotropin in hydatidiform moles is human chorionic gonadotropin. J Clin LH. In a few cases, patients have had elevated Endocrinol Metab 1975;40:482-491. FSH and LH subunits. The tumor may also 7. Cohen JD, Utiger RD: Metastatic choriocarcinoma associated with hyperthyroidism. J Clin Endocrinol Metab 1970;30:423- produce an abnormal FSH molecule that is not 429. active and therefore does not cause clinical ex- 8. Steigbigel NH, Oppenbeim JJ, Fishman LM, et al: Metasta- pression. Like TSH tumors, the gonadotropin- tic embryonal carcinoma of the testis associated with elevated producing tumors are usually autonomously plasma TSH-like activity and hyperthyroidism. N Engl J Med 1964;271:345-349. functioning with blunted or absent response 9. Valenta L, Lennarchand-Beraud T, Nemec J, et al: Metasta- to LHRH stimulation or suppression after tes- tic thyroid carcinoma provoking hyperthyroidism, with elevated tosterone administration. In a man without circulating stimulators. Am J Med 1970;48:72-76. symptoms or signs due to pituitary dysfunction 10.Hennen G: Thyrotropin-like factor in a nonendocrine can- cer tissue. Arch Int Physiol Biochem 1966;74:701-704. or size, it would be difficult to diagnose an FSH- 11.Odell WD, Wilbur JF, Utiger RD: Studies of thyrotropin secreting tumor in the early stages unless one physiology by means of radioimmunoassay. Recent Prog Horm checked sperm counts or performed a testicu- Res 1967;23:47-85. 12. lar biopsy. In women, the tumor may be sus- Hennen G: Detection and study of human chorionic thyroid stimulating factor. Arch Int Physiol Biochem 1965;73:689-695. pected earlier due to the manifestation of men- 13.Gershengorn MC, Weintraub BD: Thyrotropin-induced ses irregularities. Treatment usually consists hyperthyroidism caused by selective resistance to thyroid hor- of surgery or radiation therapy directed toward mone: A new syndrome of "inappropriate secretion of TSH."J Clin Invest 1975;56:663-642. relief of the parasellar and sellar compressive 14.Cushing H, Davidoff LM: Studies in acromegaly IV: The effect. basal metabolism. Arch Intern Med 1927;39:673-697. 15.Davis AC: Acromegaly: The thyroid gland in 166 cases of Summary acromegaly. J Clin Endocrinol 1971;1:445. 16. Because proper treatment depends on the Thompson WO, Thompson PK: Treatment of toxic goiter by irradiation of the pituitary, abstracted. J Clin Invest cause of the hyperthyroidism, identification of 1944;23:951. other etiologies is clinically relevant. As one 17.Kellett HA, Wyllie AH, Dale BA, et al: Hyperthyroidism can ascertain, hyperthyroidism and excessive due to a pituitary-secreting microadenoma. Clin Endocrinol (Oxf) 1983;19(1):57-67. TSH secretion are rare, but the number of such 18.Koide Y, Kugai N, Kimura S, et al: A case of pituitary ade- diagnoses would increase if serum TSH was noma with possible simultaneous secretion of thyrotropin and routinely measured in all patients with thyro- follicle stimulating hormone. J Clin Endocrinol Metab 1982;54:397-403. toxicosis. However, this does not appear to be 19.Wollesen F, Anderson T, Karle A: Size reduction of extrasel- cost-effective. The best present course is to con- lar pituitary tumors during bromocriptine treatment: Quanti-

Case report • Bermingham and Haenel JAOA • Vol 89 • No 12 • December 1989 • 1565 talon of effect on different types of tumor. Ann Intern Med pin induced hyperthyroidism: Use of alpha and beta subunit 1982;96:281-286. levels to identify patients with pituitary tumors. J Clin Endo- 1977;45:534-543. 20.Carlson HE, Linfoot JA, Braunstein GD, et al: Hyperthy- crinol Metab roidism and acromegaly due to a thyrotropin and growth hor- 28.Reschini E, Giustina G, Cantalamessa L, et al: Hyperthy- mone-secreting pituitary tumor: Lack of hormonal response to roidism with elevated plasma TSH and pituitary tumor: Study bromocriptine. Am J Med 1983;74:915-923. with somatostatin. J Clin Endocrinol Metab 1976;43:924-927. 21.Lamberts SWJ, Oosterom R, Verluen T, et al: Regulations 29. Pekonen F, Carayon P, Amr S, et al: Heterogeneous forms of hormone release by cultured cells from a thyrotropin growth of thyroid-stimulating hormone in mouse thyrotropic tumor and hormone-secreting pituitary tumor: Direct inhibiting effects of serum: Differences in receptor binding and adenylate cyclase- 3, 5, 3-triiodothyronine and dexamethasone on thyrotropin se- stimulating activity. Norm Metab Res 1981;13:617-620. cretion. J Endocrinol Invest 1984;7:313-317. 30.Joshi LR, Weintraub BD: Naturally occurring forms of thy- 22. Beck-Peccoz P, Piscitelli G, Amr S, et al: Endocrine, bio- rotropin with low bioactivity and altered carbohydrate content chemical and morphological studies of a pituitary adenoma se- as competitive antagonist to more bioactive forms. Endocrinol- creting growth hormone, thyrotropin (TSH) and alpha subunit: ogy 1983;113:2145. Evidence for secretion of TSH with increased bioactivity. J Clin 31. Klibanski A, Ridgway CE, Zervas NT: Pure alpha-subunit Endocrinol Metab 1986;62:704-711. secreting pituitary tumors. J Microsurg 1983;59:585-589. 23.Chanson P, Orgiazzi J, Derome PJ, et al: Paradoxical re- 32. Scanlon MF, Howells S, Peters JR, et al: Hyperprolacti- sponse of thyrotropin to L-dopa and presence of dopamineric naemia, amenorrhea and galactarrhea due to a pituitary thy- receptors in a thyrotropin-secreting pituitary adenoma. J Clin rotroph adenoma. Clin Endocrinol 1985;23:35-42. Endocrinol Metab 1984;59:542-546. 33. Wajchenberg BL, Tsanaclis AM, Marino R, Jr: TSH-con- 24. Yovos JG, Falko JM, ODorisio TM, et al: Thyrotmdcosis taining pituitary adenoma associated with primary hypothy- and a thyrotropin-secreting pituitary tumor causing unilateral roidism manifested by amenorrhea and galactorrhea. Acta En- exophthalmos. J Clin Endocrinol Metab 1981;53:338-343. docrinol 1984;106:61-66. 25.Waldhausl W, Bratusch-Marrain P, Nowotny P, et al: Sec- 34. Demurs R, Kubo 0, Demura H, et al: FSH and LH secret- ondary hyperthyroidism due to thyrotropin hypersecretion: ing pituitary adenoma. J Clin Endocrinol Metab 1977;45:653- Study of pituitary tumor morphology and thyrotropin chemis- 657. try and release. J Clin Endocrinol Metab 1979;49:879-887. 35. Woolf PD, Schenk EA: An FSH-producing pituitary tumor 26. Kaurides LA, Weintraub BD, Ridgway EC, et al: Pituitary in a patient with hypogonadism. J Clin Endocrinol Metab secretion of alpha and beta subunit of human thyrotropin in 1974;38:561-568. patients with thyroid disorders. J Clin Endocrinol Metab, 36. Snyder PJ, Sterling FH: Hypersecretion of LH and FSH by 1975;40:872-885. a pituitary adenoma. J Clin Endocrinol Metab 1976;42:544- 27.Kourides IA, Ridgway EC, Weintraub BD, et al: Thyrotro- 550.

1566 • JAOA • Vol 89 • No 12 • December 1989 Case report • Bermingham and Haenel