Neurological Problems in Endocrine Diseases

Symposium on Endocrine Disorders

Neurological Problems in Endocrine Diseases Allan J. D . Dale, MD.

Endocrine diseases are frequently associated with disorders of the neuromuscular and central nervous systems. Neurologic problems may be the main reason why a patient seeks medical attention, the underlying endocrine disease being discovered only upon careful study of the presenting complaint. It is important to recognize such neurologic cha nges because they are potentially reversible but can easily be mistaken for other neurologic diseases having a less favorable prognosis. The neurologic problem may be severe, such as hemorrhage into a pituitary tumor with acute loss of vision, or coma and myxedema, or it may develop gradually over several months, as exemplified by thyrotoxicosis with myopathy affecting the shoulder and pelvic girdle muscles.

DISORDERS OF PARATHYROID FUNCTION Hyperparathyroidism Excessive secretion of parathyroid hormone from parathyroid adenoma or hyperplasia causes hypercalcemia, which is sometimes severe. The neurologic problems encountered in hyperparathyroidism are related to this biochemical abnormality and they resolve with its correction. Common complaints are lassitude, weakness, increased irritability, and anxiety. Some patients display frank disorders of personality and mental function such as agitation, paranoid thinking, psychotic reactions, confusion, and stupor. Neuromuscular excitability, which depends upon a proper concentration of calcium ion, is reduced and in some cases true muscle weakness appears. This may be severe enough to prevent the patient from sitting or standing alone or even lifting a limb off the bed. 16 Gardner and Koppel described a hypercalcemic crisis in one patient who manifested profound muscular weakness and mental confusion which progressed to intermittent coma; this was associated with a serum calcium level of 31.2 mg/lOO ml, the highest ever recorded. The patient recovered after removal of a parathyroid adenoma. A rare complication is the development of neonatal tetany in an infant born of a mother with h yperparathyroidism. 6 This results from Medical Clinics of North America- Vol. 56, No. 4, July 1972

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suppression of the fetal parathyroid glands by the increased concentration of calcium passing through the placenta; it is transient and could be confused with other causes of neonatal tetany. Babies born of mothers with hyperparathyroidism should be carefully observed for tetany in the neonatal period. Electroencephalographic (EEG) abnormalities occur in hypercalcemia, whatever the cause. The background rhythm slows, and slow frequency theta and delta activity appears. In some patients high voltage delta activity, which is bilaterally synchronous, may be seen, especially during hyperventilation. These changes are not specific for hypercalcemia, and they usually disappear over a period of several days or weeks after its correction and disappearance of the clinical symptoms. H ypoparath yroidism Lowered serum calcium in this disease leads to increased neuromuscular excitability; transient paresthesias, muscle cramping and twitching, overt tetany with spontaneous carpopedal muscle spasms, and convulsive seizures occur. Tetany is sometimes latent and it can then be demonstrated only by maneuvers such as hyperventilation or making a limb ischemic to produce carpal spasms (Trousseau's sign), or by tapping over a peripheral nerve to cause twitching in muscles it innervates (Chvostek's sign). Papilledema and increased intracranial pressure have also been described; in this respect a brain tumor may be simulated. Symmetric calcifications in the basal ganglia are visible on the skull x-rays of some patients, and chorea may occur. Mental symptoms such as confusion, agitation or drowsiness, hallucinations, and depression may also develop. The EEG may show only slowing of background rhythms in mild cases of hypoparathyroidism but in more severe cases, slow frequency theta and delta activity becomes evident, as well as isolated sharp waves and bilaterally synchronous paroxysms of high voltage delta rhythm activity in some instances. These abnormalities are aggravated by hyperventilation.

DISORDERS OF THYROID FUNCTION Hyperthyroidism Thyrotoxicosis may be associated with disorders affecting the neuromuscular system (chronic thyrotoxic myopathy, myasthenia gravis, hypokalemic periodic paralysis), the eye (exophthalmos, external ophthalmoplegia), and the brain (acute organic brain syndrome). A sensation of easy fatigability and generalized weakness is felt by most hyperthyroid patients, but there is a true chronic thyrotoxic myopathy that is characterized by definite muscle weakness and mild atrophy of the muscles of the limb girdles, especially the pelvic girdle muscles. Because of this distribution of muscle weakness, patients particularly notice difficulty with walking, climbing stairs, and arising from low chairs. Bulbar muscles are rarely affected. Deep tendon reflexes are normal or even mildly hyperactive. Often muscle cramps occur, which are occasionally severe; in one

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reported case muscle cramps were unassociated with · increase in. the level of lactate in the venous blood after ischemic exercise. 2 This myopathy is commoner in adult males with thyrotoxicosis, and it improves with treatment of the hyperthyroidism. Myasthenia gravis and hyperthyroidism can occur together in the same patient, either simultaneously or with one preceding the other by a variable period of time, usually months. This combination is more likely in females. Diagnosis of the myasthenia gravis depends upon objective evidence of muscle weakness (particularly of bulbar muscles), the response to edrophonium chloride (Tensilon test), and electromyographic demonstration of defective neuromuscular transmission. Rarely, patients with hyperthyroidism suffer from acute thyrotoxic "myopathy" or bulbar palsy, with severe weakness involving especially the bulbar muscles; sometimes tracheostomy is necessary. This type of myopathy is usually considered to be a manifestation of myasthenia gravis. The occurrence of hypo kale mic periodic paralysis in a patient with hyperthyroidism is an example of the rare association of two distinct diseases. This particular association is more frequent in Oriental races. Periodic paralysis, latent until hyperthyroidism develops, becomes asymptomatic after treatment of the thyroid disease. These attacks of muscle weakness are no different from those of idiopathic familial hypokalemic periodic paralysis, and tend to follow a rest period after exercise or excessive carbohydrate intake. The weakness sometimes lasts many hours, and may be severe enough to cause a flaccid quadriplegia. Eye signs are common in thyrotoxicosis. They include widening of the palpebral fissures, lid lag with downward movements of the eyeballs, and exophthalmos. Exophthalmoplegia, which seems less related to the degree of exophthalmos than to primary involvement of the extraocular muscles, has a predilection for the superior recti muscle, though movements of any of the extraocular muscles may be weak. Total ophthalmoplegia is rare. Exophthalmos can occur in the absence of other clinical signs of thyrotoxicosis; at first it may be unilateral, simulating an orbital tumor or a sphenoid ridge meningioma. Occasionally, severe "malignant" exophthalmos develops, manifested by conjunctival edema (chemosis), restriction of eyeball movements, papilledema, loss of visual acuity, and visual field changes (usually a central scotoma). In order to preserve vision, such severe exophthalmos requires prompt and vigorous treatment, including surgical decompression of the orbit, or consideration of the use of massive doses of steroids. 2o While patients with thyrotoxicosis characteristically are tremulous or mildly anxious and overactive, prominent mental disturbances develop in a few. These include manic excitement and schizophrenic-like symptoms with delusions and hallucinations, depressive psychotic symptoms, and impairment of memory, orientation, and judgment. Treatment of the thyrotoxicosis is usually followed by improvement.

Hypothyroidism Myxedema frequently affects the neuromuscular system. Examples of this include slowing of the relaxation phase of deep tendon reflexes,

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muscle cramps, the carpal tunnel syndrome, muscle weakness because of a myopathy, and, infrequently, peripheral neuropathy. Muscle cramps may be frequent and severe, though clinically and electromyographically they are similar to ordinary benign muscle cramps. Percussion of muscle may cause myo-edema, that is, local "mounding" or swelling of the muscle fibers in the area percussed, which lasts several seconds. Examination by needle electrode shows that this phenomenon is electrically silent. Compression of the median nerve in the carpal tunnel at the wrist produces symptoms and signs in myxedema which are similar to carpal tunnel syndrome from any cause. Patients find that paresthesias are often poorly localized to specific fingers, and that they tend to occur at night, or while they are driving a car, holding a newspaper, or during other use of the hands. Vigorous shaking of the hands usually affords temporary relief. Sharp percussion of the median nerve at the wrist causes tingling sensations in the first three fingers (Tinel's phenomenon). Muscle weakness and atrophy develop in thenar muscles innervated by the median nerve. Since treatment of these patients with thyroid hormone is likely to correct the carpal tunnel syndrome, surgical decompression should be deferred unless compression of the median nerve has been severe, or hormone replacement therapy is ineffective. Muscle weakness resulting from hypothyroid myopathy is generalized, but it is most prominent in the shoulder and pelvic girdle muscles.17 Muscle aching, cramps, and bulkiness of muscles may be associated with it. Microscopic study of muscle tissue may show structural alterations such as vacuoles, abnormal oxidative enzyme activity, glycogen deposits, mitochondrial changes, and some fiber atrophy.13 The existence of peripheral neuropathy resulting from myxedema is suggested by evidence in some reports. 5 , 8 Paresthesias in the distallimbs, variously described as tingling, numbness, and burning, occur and slowing of nerve conduction velocities may be demonstrated. Changes in personality, memory, and intellectual function occur in myxedema. In some patients these are prominent, and comprise the so-called myxedema madness, which may simulate major psychiatric or organic brain disease. True cerebellar ataxia, particularly affecting gait, has also been observed in myxedema, either of primary thyroid or of pituitary origin. Definite and usually prompt improvement from thyroid hormone treatment is usual. Myxedema coma is a medical emergency.4, 9, 21 Mortality has always been high, at least 50 per cent, even in the best of series. Stresses such as infection or anesthesia are important precipitating factors; more than half of the cases develop after admission to hospital for some other reason. The typical patient is an elderly woman. Coma develops gradually over a period of hours, rather than abruptly, and the profound disturbance of consciousness probably results from complicating factors such as hypothermia, alveolar hypoventilation with respiratory acidosis, and water retention with hyponatremia from inappropriate ADH secretion. The effect of a low level of thyroid hormone upon the brain seems less likely to be the cause of coma. Hypothermia may be profound and if the

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patient's temperature is less than 90 F (32.2 C), the prognosis is grave. Rapid replacement of thyroid hormone in adequate amounts (e.g., intravenous levothyroxine in doses of 400 to 500 ILg ) is mandatory, and antibiotics, fluid restriction, respiratory assistance when indicated, and often steroid medication are important. DISORDERS OF ADRENAL FUNCTION The Adrenal Cortex ADRENAL CORTICAL INSUFFICIENCY. Patients with the chronic form (Addison's disease) often have mild mental symptoms such as apathy, easy fatigability, anxiety, and irritability. Occasionally psychotic reactions, such as manic depressive states, paranoid reactions, or catatonic states develop. Mental and neurologic symptoms can also result from associated hypoglycemia. In a few patients with Addison's disease, true flaccid paralysis of limb and trunk muscles has occurred, presumably being related to hyperkalemia. 24 It may be periodic, and treatment with intravenous glucose, with or without insulin, and steroids has been effective. Heat cramps may occur more readily in Addison's disease; these are related to the dehydration and salt depletion of excessive sweating in a hot environment. The EEG, which is within normal limits in mild cases of Addison's disease, becomes abnormal in more severe disease and during crises of acute adrenal cortical insufficiency whatever the cause. The normal background rhythm becomes slower, and if coma develops in a severe crisis, generalized slow frequency delta activity ensues. Administration of corticosteroids rapidly improves the EEG changes. HYPERFUNCTION OF THE ADRENAL CORTEX. Mild mental symptoms such as insomnia, anxiety, hyperactivity, and restlessness are common in Cushing's syndrome. Sometimes severe psychotic reactions, with paranoid delusions and auditory hallucinations, occur. Diffuse nonspecific muscle weakness is frequently noticed, and some patients present myopathy with limb girdle muscle weakness and mild atrophy. Serum creatine phosphokinase and glutamic-oxalacetic transaminase levels are not usually elevated. Administration of synthetic steroids, especially the fluorinated compounds such as triamcinolone and dexamethasone, is sometimes followed by myopathy which improves slowly after therapy is stopped. PRIMARY ALDOSTERONISM. This most often results from excessive secretion of aldosterone by an adenoma of the adrenal cortex. Hypokalemia, hypernatremia, and alkalosis are characteristic. Recurrent attacks of generalized muscular weakness related to severe hypokalemia and simulating familial periodic paralysis have been reported. Removal of the tumor is followed by disappearance of such attacks. Adrenal Medulla PHEOCHROMOCYTOMA. This tumor of the adrenal medulla (usually histologically benign but a carcinoma in 10 per cent of cases) secretes

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increased quantities of epinephrine and norepinephrine. Sustained or paroxysmal hypertension results. Episodes of sudden paroxysmal hypertension occur in approximately half the patients, and are often caused by physical exertion or changes in posture or by manipulation of the tumor during physical examination of the abdomen or during surgery. The paroxysms are characterized by severe throbbing generalized headache, pallor, perspiration, and severe anxiety; if the attack is severe, cerebral hemorrhage and death may occur.2:1

DISORDERS OF PANCREATIC FUNCTION Diabetes DIABETIC COMA. The most serious neurologic problem in disorders of pancreatic function is coma. This may be due to either diabetic acidosis or hypo glycemia. Rapid and accurate differentiation of the type of coma, and exclusion of intracranial disorder, is vital to prevent permanent brain damage. Clinical differentiation between the two types of coma is difficult, and occasionally insulin shock has been inadvertently treated with insulin. Unless hypoglycemic coma has been so prolonged as to cause irreversible brain damage, intravenous injection of glucose rapidly returns these patients to normal. The coma of diabetic acidosis usually follows stress such as infection, surgery, or trauma, or it may be caused by inadvertent interruption in the regular daily dose of insulin. In a few patients, acidosis and coma are the first manifestations of diabetes mellitus; consequently the situation may not be recognized and a fatal outcome may ensue. Feelings of fatigue, generalized weakness, dull headache, epigastric abdominal pain (sometimes severe), and nausea and vomiting signal the onset of diabetic acidosis. Insatiable thirst and the excretion of large volumes of urine are noticed. Then increasing lethargy or restlessness followed by stupor, and deep sighing respiration (Kussmaul breathing) develop. Coma supervenes, perhaps in a few hours; the patient is dehydrated as evidenced by the dry mucous membranes and skin, and loss of normal skin turgor. Oliguria, hypotension, rapid feeble pulse, and the characteristic odor of acetone on the breath precede circulatory collapse, anuria, and death. Examination of the cerebrospinal fluid reveals no abnormalities except an increase in glucose which reflects the increased blood glucose level. The EEG becomes increasingly abnormal with slowing of the background rhythms and the development of slow frequency (theta and delta) activity. Even after effective treatment return to normal rhythm is not likely for several days. HYPOGLYCEMIC COMA. Like hypoxia, hypoglycemia quickly produces serious changes in brain function, the gray matter being more vulnerable than the white matter; permanent brain damage ensues if hypoglycemia is not quickly corrected. The level of blood glucose at which symptoms appear varies, and the rate of fall may be as important as the actual level in determining the intensity of the symptoms. Hypoglycemic episodes are most often due to excessive secretion of insulin by a pan-

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creatic islet cell tumor or to inappropriate management of a diabetic patient. A hypoglycemic attack may occur any time but it is most common in the early morning hours or after exercise. Attacks may be episodic, becoming increasingly severe and frequent in patients who have pancreatic islet cell tumors.· Premonitory symptoms (which do not always occur in every patient) include feelings of hunger, nausea, sweating, apprehension, restlessness, or lethargy. With progressive decrease of the blood glucose level, disorientation, confusion, hallucinations, extreme restlessness or agitation, pallor, and tachycardia result. Diplopia, grand mal or focal seizures, myoclonic jerks, and hyperrefiexia with clonus and Babinski responses may be other features. Stupor, then coma, may follow quickly. The cerebrospinal fiuid is normal except for a decreased glucose content, consistent with hypo glycemia. The EEG shows slowing of normal rhythm, and there is increased sensitivity to hyperventilation; generalized slow delta frequencies develop in coma. Hypoglycemia is a potent activator of epileptiform activity, and spike discharges or spike and slow wave activity may be recorded. With correction of hypo glycemia, the EEG may return to normal within minutes, but in cases of severe coma improvement may take hours and even several days. If the brain has been damaged irreversibly, disorganized and slower frequency activity may persist. The treatment consists of rapid intravenous administration of glucose; at least 10 ml of a 50 per cent glucose solution should be injected. Before this, however, blood must be taken for determination of the blood glucose level. NEUROPATHY. Diffuse peripheral neuropathy is a common complication of diabetes mellitus. Its severity and course often do not parallel the adequacy of control of blood sugar levels or the duration of the diabetes mellitus. Symptoms include paresthesias or burning dysesthesias affecting the extremities and examination reveals impairment of sensation, hyporefiexia, and sometimes mild weakness of distal muscles of the limbs. Neuropathy may become severe and disabling, and it may be associated with abnormalities of autonomic nervous system function such as diarrhea, constipation, pupillary changes, anhidrosis, impotence, and orthostatic hypotension. Patients who show no clinical evidence of peripheral neuropathy may have slowing of nerve conduction when electromyography is done, indicating subclinical involvement of the peripheral nerves. 15 Lesions of single peripheral nerves (e.g., involving the femoral, peroneal, oculomotor, or abducens nerves), a spinal nerve root, or a limb plexus can develop, sometimes abruptly, and pain may be great. Spontaneous improvement over a period of several months is frequent.

Islet Cell Tumors HYPERINSULINISM NEURONOPATHY. Some patients with spontaneous hypo glycemia present with a syndrome of progressive symmetric

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weakness and muscular atrophy, especially of small muscles of the hands, paresthesias in distal portions of the limbs, hyporefiexia, and sometimes muscle fasciculations. This is almost always associated with a pancreatic islet cell tumor. It seems likely that both the peripheral nerves and the anterior horn cells are involved, and so the term "hyperinsulin neuronopathy" has been proposed. 14 The clinical picture usually becomes apparent after the hypoglycemic episodes have begun. Removal of the islet cell tumor is followed by slow improvement.

DISORDERS OF THE PITUITARY AND HYPOTHALAMUS The pituitary gland and the overlying hypothalamus - which are intimately related to the optic chiasm, optic nerves and tracts, the third, fourth, and sixth cranial nerves in the cavernous sinuses, and the internal carotid arteries and their major branches-are affected by many lesions. Tumors of the pituitary constitute 10 per cent of all intracranial tumors. Pituitary chromophobe adenomas and craniopharyngiomas are the most common but primary and secondary pituitary carcinomas 2o , 22 and sarcomas,11 pituitary eosinophilic and basophilic adenomas, meningiomas of the tuberculum sellae and clinoid processes, and clivus chordomas are all encountered. Chromophobe adenomas vary from small symptomless tumors to huge ones which may expand in any direction; they may then involve the hypothalamus, basal portions of the cerebral hemispheres, the sphenoid sinus, or the cavernous sinuses and related structures. Craniopharyngiomas, arising from the epithelial remnants of the hypophyseal duct (Rathke's pouch), can present at any time during life, to cause hypopituitarism, diabetes insipidus, visual field changes, or dementia. Other disorders may affect this region: these include granulomas (sarcoidosis, tuberculosis, Hand-Schuller-Christian disease), hemorrhage and infarction (occurring spontaneously in a tumor, resulting from head trauma, or following rupture of a congenital aneurysm), aneurysms of the internal carotid artery (which compress the pituitary gland), and infectious diseases. The most important neurologic problem associated with any of these lesions is impairment of vision from involvement of the optic chiasm, nerves, and tracts. It is a not uncommon and sometimes tragic error to delay identification of the cause of "blurred vision" because several "changes in glasses" were tried first. Early recognition is of paramount importance in order to preserve maximal visual function. Characteristically, compression of the optic chiasm causes a defect in the temporal half of one or both visual fields (bitemporal hemianopsia). This initially affects the upper portion of the temporal area, if compression is due to a lesion in the underlying pituitary gland. Bitemporal hemianopsia indicates involvement of the optic chiasm in all cases, except when there is raised intracranial pressure resulting from a lesion elsewhere which is causing obstructive hydrocephalus. Then, dilation of the third ventricle compresses the optic chiasm from above producing a bitemporal hemianopsia, which is then a false localizing sign.

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Headaches are not prominent symptoms in patients with expanding lesions in the pituitary-hypo thalamic area unless these lesions become large enough to cause raised intracranial pressure with its characteristic pattern of headache. Rarely, spontaneous hemorrhage occurs into a pituitary tumor (it is sometimes the initial manifestation); headache is then sudden, severe, and generalized, and associated with rapid visual impairment, confusion, and even coma.19 . 27 This emergency demands consideration of prompt neurosurgical intervention. Other neurologic problems may include the following: diplopia from compression of the third, fourth, or sixth cranial nerves; spontaneous cerebrospinal fluid rhinorrhea and the risk of recurrent bacterial meningitis (if the tumor extends downward into the sphenoid sinus);1 and, from hypo thalamic involvement, sleep disturbances, marked emotional ability or inappropriate rage reactions,12. 18 diabetes insipidus, inappropriate ADH secretion, and changes in appetite causing severe inanition or obesity.26 A large lesion such as a craniopharyngioma may cause impairment of memory and intellect, presumably from compression of the overlying basal frontal and temporal lobes ;:) surgical decompression or removal can alleviate these mental changes. Since different lesions in this region may produce similar signs and symptoms and endocrine disorders, radiologic examination often provides the most reliable differential diagnosis. Among patients with craniopharyngiomas, 70 to 80 per cent show some evidence of calcification above the sella turcica. Curvilinear deposits of calcium may suggest a cyst or an aneurysm in the area. Enlargement of the sella turcica, or erosion of its floor or of the posterior clinoid processes and dorsum sellae, occurs with tumors in the pituitary-hypo thalamic area. The EEG , echoencephalogram, and radioactive brain scan7 are of little assistance since the lesions are small and lie deep in the middle of the head. Unless there is associated acute subarachnoid hemorrhage or infectious meningitis, cerebrospinal fluid examination is not helpful. Cerebral angiography and pneumoencephalography usually disclose the final localization and identification of a tumor or vascular lesion. Those patients in whom an enlarged sella turcica is visible roentgenographically and in whom there is pituitary hypofunction yet no visual impairment or any other neurologic problem must be followed regularly at 6 to 12 month intervals. Detailed visual field examinations as well as skull x-ray examinations are essential for comparison with previous results. The patient must understand that any visual impairment requires immediate evaluation. Only by such careful observation can severe irreversible damage to the visual apparatus be prevented.

DIFFERENTIAL DIAGNOSIS To conclude this review, the important types of neurologic disorders in endocrine diseases will be briefly summarized by emphasizing the diagnostic possibilities they may suggest. Coma may complicate hypoglycemia, diabetic acidosis, CrISIS in adrenocortical insufficiency, myxedema, or severe hypercalcemia. A

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careful and detailed history and examination are mandatory. Immediate administration of glucose intravenously is necessary if coma is possibly the result of hypo glycemia, because it is associated with the greatest risk of permanent brain damage. Disorders of memory, intellectual junction, and personality attend many endocrine disorders. Psychotic reactions can occur in thyrotoxicosis, myxedema, Cushing's syndrome, hypercalcemia, hypo glycemia, and Addison's disease. Examination may also detect features of an organic brain syndrome such as disorientation, and impairment of recent memory and intellect. Since these are potentially reversible changes, patients presenting with "senility" or "psychosis" deserve at least minimal investigation of their endocrine status. Neuromuscular disorders, such as progressive limb girdle muscle weakness, peripheral neuropathy, muscle cramps, and intermittent severe generalized muscle weakness may be prominent features of endocrine disorders. Careful history and examination, with basic investigative procedures for blood sugar, serum thyroxine, calcium, and potassium, and also electromyographic examination, are necessary. The term "limb girdle muscular dystrophy" has been found to cover many types of myopathy, including endocrine myopathies; a diagnosis of "muscular dystrophy" can only be made after careful study, including muscle biopsy if needed. Proper treatment of an underlying endocrine disorder leads to a gratifying improvement in associated neuromuscular disorders. Electroencephalographic abnormalities are common with severe metabolic derangements. The electrical changes are nonspecific and, alone, they do not allow diagnosis of the underlying disease. Slowing of the background rhythms is common, and with severe metabolic changes or coma, generalized slow frequency theta or delta activity supervenes. Focal abnormalities are not to be expected, and epileptiform discharges are likely to be seen only during episodes of hypo glycemia or severe hypocalcemia.

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11. Greenhouse AH: Pituitary sarcoma: a possible consequence of radiation. JAMA 190:269-273, 1964 12. Killeffer FA, Stern WE: Chronic effects of hypothalamic injury: report of a case of near total hypothalmic destruction resulting from removal of a craniopharyngioma. Arch Neurol 22:419-429, 1970 13. Lambert EH, Sayre GP: Myopathy in rabbits following thyroidectomy (abstract). Am J Physiol 183:636-637, 1955 14. Mulder DW, Bastron JA, Lambert EH: Hyperinsulin neuronopathy. Neurology 6:627-635, 1956 15. Mulder DW, Lambert EH, Bastron JA, et al: The neuropathies associated with diabetes mellitus: a clinical and electromyographic study of 103 unselected diabetic patients. Neurology 11 :275-284, 1961 16. Murphy TR, ReMine WH, Burbank MK: Hyperparathyroidism: report of a case in which parathyroid adenoma presented primarily with profound muscular weakness. Mayo Clin Proc 35:629-634, 1960 17. Norris FH Jr, Panner BJ: Hypothyroid myopathy: clinical, electromyographical, and ultrastructural observations. Arch Neurol 14:574-589, 1966 18. Reeves AG, Plum F: Hyperphagia, rage, and dementia accompanying a ventromedial hypothalamic neoplasm. Arch Neurol 20:616-624, 1969 19. Robinson JL: Sudden blindness with pituitary tumors: report of three cases. J Neurosurg 36:83-85, 1972 20. Scholz DA, Gastineau CF, Harrison EG Jr: Cushing's syndrome with malignant chromophobe tumor of the pituitary and extracranial metastasis: report of case. Mayo Clin Proc 37:31-42, 1962 21. Senior RM, Birge SJ, Wessler S, et al: The recognition and management of myxedema coma. JAMA 217:61-65, 1971 22. Solitare GB, Jatlow T: Adenohypophysial carcinoma: case report. J Neurosurg 26:624-632, 1967 23. Thomas JE, Rooke ED, Kvale WF: The neurologist's experience with pheochromocytoma: a review of 100 cases. JAMA 197:754-758, 1966 24. Van Dellen RG, Purnell DC: Hyperkalemic paralysis in Addison's disease. Mayo Clin Proc 44:904-914, 1969 25. Werner SC: Prednisone in emergency treatment of malignant exophthalmos. Lancet 1:1004-1007,1966 26. White PT, Ross AT: Inanition syndrome in infants with anterior hypothalamic neoplasms. Neurology 13:974-981, 1963 27. Wright RL, Ojemann RG, Drew JH: Hemorrhage into pituitary adenomata. Arch Neurol 12:326-331, 1965 Mayo Clinic Rochester, Minnesota 55901