Pituitary tumor and myalgia

Generalized myalgia with painful, tender muscles as a major presenting complaint usually reflects an acute infectious process, most often viral in etiology Robert S. Kunkel, M.D. and requires no extensive diagnostic studies. Symp-

Department of Internal Medicine toms usually abate rapidly and prompt recovery is the rule. , another cause of muscle , usually is readily diagnosed because of the symptoms, A. V. Black, M.D.* elevated acute phase reactants in the blood, and abnormal muscle biopsy. Within a period of a few months we examined two patients with muscle pain and aching, and who were found to have pituitary tumors with multiple endocrine deficiencies. Our purpose in reporting these cases is to point out that endocrine dysfunction can be the cause of profound muscle symptoms and also to suggest that pituitary lesions should be considered when anyone has muscle com- plaints secondary to endocrine dysfunction.

Case reports Case 1. A 46-year-old man became ill about June 1, 1972. He began to notice pain in his calves when walking. Shortly thereafter he experienced aching discomfort in his back and shoulder muscles. He also noted weakness of his shoulders and thighs. He became anorectic and the weak- * Address: 11 North Main Street, ness progressed. He also had occasional, intermittent dull Centerville, Ohio 45459. aching pain on the left side of his head. Initial studies

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Downloaded from www.ccjm.org on September 29, 2021. For personal use only. All other uses require permission. 18 Cleveland Clinic Quarterly Vol. 43, No. 1 revealed a mild decrease in hemoglobin value hydroxycorticoids were 1.8 ng/2A hr (normal, and an enlarged sella on roentgenographic 3-12 yug/24 hr). There was no significant examination. Visual fields were normal. He increase during 2 days' use of metapyrone. was referred to the Cleveland Clinic for With ACTH stimulation, the 17-ketosteroids further evaluation. He had had a successful rose to 23.5 ng/24 hr and 17-hydroxycor- mammary artery implant for coronary artery ticoids rose to 37.4 ¿ig/24 hr. The plasma in February 1968. Prior to the current Cortisol rose to 55.2 /xg/dl after ACTH was illness he had walked 2 miles daily without given intravenously. Serum FSH was 27.4 experiencing chest pain. jjg/dl (normal, 9-40 /ig/dl). Serum LH was When seen at the Cleveland Clinic in July 1.3 ng/dl (normal, 1.8-13.0). Serum TSH 1972, approximately 6 weeks after the onset of was less than 2 microunits/ml (normal, 0-15). his illness, he had a weight loss of 8.2 kg. His Testosterone was 131 ng% (normal, 200 to main complaint was pain in the shoulders and 1000). legs which increased with movement. Exami- A pneumoencephalogram revealed a pitui- nation showed weakness of the triceps, biceps, tary tumor with 4 to 5 mm of suprasellar deltoid, and quadriceps muscle groups. Atro- bulge. He was treated with cobalt-60 and phy was evident in the shoulder girdle mus- replacement therapy consisted of cortisone cles. The neurologic examination was other- acetate, testosterone, and thyroid. He had wise normal. The visual fields were again prompt and complete relief of all myalgic normal. Results of the following laboratory symptoms. tests were normal: sedimentation rate, urinal- Case 2. A 55-year-old woman had under- ysis, creatine phosphokinase (CPK), lactic gone right radical mastectomy in 1968 for dehydrogenase (LDH), serum glutamic ox- carcinoma of the breast. She was in good aloacetic transaminase (SGOT), aldolase, so- health otherwise until June 1972 when she dium, chloride, potassium, immunoglobulins, began to notice soreness and aching in the serum protein electrophoresis, antinuclear fac- muscles of her neck, shoulders, and arms. She tor, and LE test. The PBI was 5.2 ng/dl, Ts could remember no antecedent illness. A phys- red cell uptake (tesitope) 29.7%, and effective ician found her to be mildly anemic and she thyroxine ratio 0.92. All these thyroid values was treated with vitamin BI2 and iron with no were in the lower range of normal. The abatement of symptoms. A hematologist ex- hemoglobin was 12.3 g/dl, hematocrit 36.5%, amined her in October 1972 and found that and white blood cell (WBC) count 3,200/cu she had . She was given thy- mm with a normal differential count. An elec- roid replacement. When examined on De- tromyogram was within normal limits as was cember 15, she had tachycardia, pedal edema, a muscle biopsy of the left vastus lateralis. and bilateral basilar rales. Thyroid therapy Roentgenograms of the entire gastrointestinal was stopped and she was treated with digitalis tract, an intravenous urogram, and chest films and diuretics. She had lost 9.1 kg between were normal. Roentgenograms of the skull June and December and continued to com- showed enlargement of the sella turcica with plain of sore, tender, aching muscles, the most erosion of the floor and dorsum sella. severe symptoms being in the proximal muscle groups. She also complained of blurred vision Having excluded an active inflammatory at that time and reported that she had had a process of the muscles, extensive evaluation of mild right-sided for the previous 2 pituitary function revealed evidence of ACTH, months. luteinizing hormone (LH), and thyroid- stimulating hormone (TSH) deficiencies. A Because of the visual symptoms, skull films low normal level of follicle-stimulating hor- were done which showed an enlarged sella mone (FSH) was present. Plasma Cortisol was turcica; visual field examination revealed bi- 3.6 jug/dl at 4:00 p.m. and 8:00 a.m. (normal, temporal field loss, more on the right. One 6-26 fig/dl). Urinary 17-ketosteroids were 4.5 week later, the field defects had progressed. mg/24 hr (normal, 6-21 mg/24 hr), 17- She was referred to the Cleveland Clinic for

Downloaded from www.ccjm.org on September 29, 2021. For personal use only. All other uses require permission. Spring 1976 Pituitary tumor and myalgia 19 definitive study and treatment. When exam- completely free of pain, had no headache, and ined on January 6, 1973, she denied having generally felt well. Visual fields were com- polyuria and salt craving, but did notice some pletely within normal limits. She was seen increased thirst. She complained of fatigue and again 1 year after the operation and was muscle aching. She stated that her last men- completely asymptomatic. She was taking the strual period had been in 1971. On examina- sodium levothyroxine and cortisone acetate as tion her blood pressure was 120/60 mm Hg, prescribed. and pulse rate was 78. Results of physical examination were normal except for the right Discussion visual field defect, the absence of the right breast, and of the proximal mus- In recent years there has been increas- cles. There was no atrophy, but the strength of ing interest in endocrine causes of myopa- the proximal muscles of the shoulder and thy with thyroid dysfunction being impli- pelvic girdle was slightly diminished. cated most often.1"8 Proximal muscle Laboratory studies disclosed the following weakness is a common finding in thyro- values: hemoglobin, 11.5 g/dl; hematocrit, toxicosis, and it has been stated that 33.2%; and WBC 4, 100/cu mm. Differential proximal is present and can be count, 27% polymorphonuclear cells, 25% demonstrated in all patients with eosinophils, 39% lymphocytes, and 9% mono- thyrotoxicosis.6 is also a cytes. Plasma Cortisol at 8:15 a.m. was 1.8 «g/dl (normal, 6-26 «g/dl); the PBI, 4.6 common complaint in persons with hypothyroidism.1-5 Pain in the form of Mg/dl; T3 red cell uptake, 24.6% (normal, 25%-35%); and the effective thyroxine ratio generalized aching and also occurring as 0.85 (normal, 0.86-1.13). The serum potas- with muscle contraction is said to sium was 4.3 mEq/liter; sodium, 143 mEq/ be less well appreciated as a symptom of liter; and the chloride, 104 mEq/liter. A glu- hypothyroidism.4 However, aching cose tolerance test was normal. The 24-hour in muscles are not infrequent and muscle urine for 17-ketosteroids revealed 3.0 mg/24 action may be painful. Collins et al,8 in a hr, the 17-hydroxycorticoids being 0.9 mg/24 review of 75 cases of hypothyroidism, hr; both values quite low. The 24-hr urine for gonadotrophin assay showed less than 13 mentioned that 72 % of patients had neu- mouse units, also low. Serum LH was less romuscular symptoms. He specifically than 1 «g/dl and the serum FSH was 23.7 listed pain in extremities as occurring in «g/dl. Roentgenograms of the skull showed 29% and muscle cramps or stiffness in erosion of the floor and dorsum of the sella 20% of 75 patients. Nevertheless, we turcica. Chest films and a brain scan were agree with Golding4 that muscular pain is normal. Visual fields confirmed superior and not very often thought of as a presenting lateral field loss on the right and superior field symptom of hypothyroidism. loss on the left. is usually accom- Carotid angiography and a pneumoenceph- panied by fatigue, muscle weakness, and alogram confirmed the presence of an intrasel- muscle wasting. Pain, however, is not a lar mass with suprasellar extension. Crani- part of Addison's disease or secondary otomy with removal of a cystic chromophobe adrenal insufficiency except for cramping adenoma was performed on January 12, 1973. The patient was discharged on a regimen of in the muscles. The cramping of muscles sodium levothyroxine (Synthroid), 0.15 mg a in patients with adrenal insufficiency is day; cortisone acetate, 25 mg in the morning believed to be due to abnormalities in and 12.5 mg in the evening; and diphenyl- electrolytes.9 hydantoin (Dilantin) 100 mg three times Other endocrinopathies are associated daily. When seen 3 months later she was with myopathy. Acromegaly is commonly

Downloaded from www.ccjm.org on September 29, 2021. For personal use only. All other uses require permission. 20 Cleveland Clinic Quarterly Vol. 43, No. 1 associated with weakness and a myopathy ered in anyone who has muscle symp- has been demonstrated.10 Myalgia or toms. If evidence of endocrine abnormali- pain, however, was not mentioned as a ties is found, we suggest a roentgenogram symptom in the 11 patients studied. Myo- of the skull and other studies to determine pathy also occurs commonly in Cushing's whether a pituitary lesion is present. disease, but pain is not a feature.11 is also known to be accompanied by a myopathy as well as recognized References neuropathy.12 1. Wilson J, Walton JN: Some muscular manifes- The myopathy and myalgia in our two tations of hypothyroidism. J Neurol Neurosurg patients was most likely due to hypothy- Psychiat 22: 320-324, 1959. roidism rather than to any of the other 2. Astrom KE, Kugelburg E, Müller R: Hypothy- endocrine deficiencies present. In these roid myopathy. Arch Neurol 5: 472-482, 1961. 3. Fessel WJ: Myopathy of hypothyroidism. Ann two instances the thyroid deficiency was Rheum Dis 27: 590-596, 1968. . due to a pituitary tumor with low levels of 4. Golding DN: Hypothyroidism presenting with 13 TSH. Dubansky et al reviewed 20 cases musculoskeletal symptoms. Ann Rheum Dis of hypothyroidism with muscular symp- 29: 10-14, 1970. toms and six of these patients had second- 5. Nickel SN, Frame B, Bebin J, et al: Myxedema neuropathy and myopathy; a clinical and path- ary hypothyroidism. Five of these six ologic study. 11: 125-137, 1961. with hypothyroidism secondary to pitui- 6. Ramsay ID: Electromyography in thyrotoxico- tary lesions had muscular pain as a sis. QJ Med 34: 255-267, 1965. prominent symptom. In a recent study by 7. Werner S, Ingebar SH, eds: The Thyroid. A Faglia et al,14 it was suggested that the Fundamental and Clinical Text, ed 3. New York, Harper and Row, 1971. incidence of impaired endocrinological 8. Collins JA Jr, Zimmer FE, Johnson WJ, et al: test results is greater in patients with The many faces of hypothyroidism. Postgrad pituitary tumors with suprasellar spread Med 36: 371-384, 1964. than in intrasellar tumors. This is 9. Williams RH: Textbook of Endocrinology, ed thought to be due to hypothalamic in- 4. Philadelphia, WB Saunders, 1968, p 320. 10. Mastalgia FL, Barwick DD, Hall R: Myopa- volvement. thy in acromegaly. Lancet 2: 907-909, 1970. 11. Müller R, Kugelberg E: Myopathy in Cush- Summary ing's syndrome. J Neurol Neurosurg Psychiat Within a few months two patients were 22: 314-319, 1959. examined who had pituitary tumors with 12. Beeson PB, McDermott W, eds: Textbook of Medicine, ed 14. Philadelphia, WB Saunders, secondary endocrine deficiencies. The 1975. main complaints of both patients were 13. Dubansky B, Svoboda E, Wiedermann M: muscle pain, soreness, and tenderness. Kontraktilitä'tsstörungen als konstantes Mus- There was no evidence of a primary kelsymptom bei der Hypothyreose. Nervenarzt muscle disorder, and the patients' symp- 28: 61-65, 1957. 14. Faglia G, Ambrosi B, Beck-Peccoz P, et al: toms responded to endocrine replacement Hypothalamic-pituitary-adrenal function in pa- therapy. Endocrine dysfunction, particu- tients with pituitary tumors. Acta Endoer 73: larly hypothyroidism, should be consid- 223-232,1973.

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