Pituitary tumors are tumors arising from remnant cells of the anterior and posterior pituitary lobes and the epithelium of the craniopharyngeal duct. In humans, the interface of neuroendocrine neurons is the hypothalamus and the pituitary gland, both of which form a unit that controls the function and broad physiological activity of several classical endocrine glands such as the thyroid, adrenal and gonads. The nervous system and the endocrine system interact, in that the activity of the endocrine glands in the human organism is regulated by the nervous system, while the hormones secreted by the endocrine glands in turn act on the central nervous system to regulate the function of the nervous system. Due to the close connection between various systems and atypical clinical manifestations, other diseases are often misdiagnosed as pituitary tumors and even surgically treated; some pituitary tumors are misdiagnosed as other diseases and are only realized when the disease is serious or causes permanent damage. The misdiagnosis and mistreatment of “pituitary tumor” in recent years are analyzed here.
1.Misdiagnosis as pituitary tumor Those who are misdiagnosed as pituitary tumor are mostly seen in primary hypothyroidism. There are also cases of hypotonia, amenorrhea, menstrual disorders, and hypogonadism; some patients show loss of vision, dizziness, palpitations or headache, nausea, vomiting, etc. Physical examination may show that the thyroid gland is not enlarged or is Ⅰ-Ⅱ degree enlarged, without pressure pain. It has been reported that hypothyroidism occurs in children before puberty, i.e. juvenile hypothyroidism is misdiagnosed as pituitary tumor, which is mostly characterized by growth retardation or short stature with weight gain, edema, hypermobility and coldness, etc. There are also other occupational lesions in the saddle area misdiagnosed as pituitary tumor. Rao reported that 6% of patients with pituitary tumors (magnetic resonance imaging (MRI) of the pituitary gland suggested pituitary “adenoma”) who underwent CAG had vascular disease.
In patients with pituitary enlargement caused by long-term hypothyroidism, almost all have typical signs and symptoms of thyroid hormone deficiency, with elevated serum TSH levels and low thyroid hormone levels, so the diagnosis should not be very difficult. However, in clinical practice, pituitary hyperplasia caused by hypothyroidism is often mistaken for pituitary tumor and surgically removed, resulting in low pituitary function. The clinical manifestations of primary hypothyroidism are diverse, including headache, dizziness, slow movement, slurred speech, visual impairment, memory loss, and fatigue, etc. The pituitary gland can be weakened by negative feedback regulation mechanism, resulting in pituitary hyperplasia and adenoma. Hypothyroidism is regulated by the hypothalamus (TRH) and the pituitary gland (TSH), and a decrease in TH weakens the negative feedback inhibition of the pituitary gland, resulting in hyperplasia and hypertrophy of TSH cells, which can lead to enlargement of the pituitary gland or even adenoma, while the surgical pathology confirms that the pituitary TSH cells are hyperplastic, In hypoparathyroidism, hypothalamic dopamine level or activity of hypothalamus causes elevated PRL and TSH. Diagnosis and laboratory tests, imaging examinations (including X-ray, CT and MRI) show pituitary occupancy, while laboratory tests report elevated TSH levels, which are easily misdiagnosed as TSH-secreting tumors of the pituitary gland.
Juvenile hypothyroidism mainly affects the growth and development of children, manifesting as delayed bone age and growth retardation, often accompanied by delayed sexual development, resulting in short stature and sexual infantilism. The main reason for misdiagnosis is the lack of proper understanding. Pituitary adenomas caused by long-term hypothyroidism are mostly seen in children, which may be related to the insidious onset and slow development of hypothyroidism, which is not easily detected by parents, and the limited expression of children and the long-term lack of treatment. The history was not detailed enough, and the symptoms and signs were not analyzed in detail. Due to the limited expression of children, the symptoms of juvenile hypothyroidism, such as inactivity, fear of cold, constipation, weight gain, etc., are not specific enough and are often ignored by parents and clinicians.
The misdiagnosis of other lesions in the saddle area as pituitary tumor indicates that endocrine function changes and vision changes in the pituitary gland are not always occupational changes in the pituitary gland, such as hypothalamic dysfunction, severe hydrocephalus, traumatic anterior skull base fracture, internal carotid artery cavernous sinus fistula and so on. More than 90% of the tumors in the saddle area are pituitary tumors, followed by craniopharyngioma, glioma, meningioma, germ cell tumor, teratoma, epithelioid cyst, chordoma, metastatic tumor, etc., which should be carefully analyzed by combining the patient’s medical history, clinical manifestations and making full use of the existing auxiliary examinations.
2.Pituitary tumor misdiagnosis Clinical reports show that the diagnosis of pituitary tumor is optic neuritis, glaucoma, ischemic optic neuropathy, optic nerve atrophy, ocular muscle paralysis syndrome, etc. However, due to the normal anatomical variation of the region and the different growth sites and development speed of the tumor, as well as the different understanding and cooperation of patients in modern visual field examination, sometimes the results of visual field examination also lack characteristics, especially the double-centered or paracentral dark spot visual field. In some cases, the result of visual field examination is not characteristic, especially the bicentric or paracentric dark spot visual field. The reason for the misdiagnosis is the one-sided belief that the visual field of pituitary tumor should be bi-temporal hemianopia, without knowing that the tumor’s compressive damage to the visual cross is progressive. Most of the patients consult the ophthalmology department because of the first symptom of vision loss. The receiving physicians only consider the diseases related to this department and neglect to ask about the endocrine history. In early pituitary tumors, local edema and blood supply are impaired, and there are no organic changes in visual fibers. Some patients with bilateral temporal hemianopia were first diagnosed with retrobulbar optic neuritis, but their vision improved after glucocorticoid or antibiotic treatment, making the doctors blindly optimistic that the diagnosis and treatment were proper, while ignoring the typical visual field changes of pituitary tumors. It is believed that as long as the visual field defect shows a vertical demarcation line, whether bilateral or monocular temporal hemianopia, it is a strong evidence of cross-visual pathology. Therefore, once temporal hemianopia is detected, attention should be paid to exclude intracranial occupying lesions. The visual field defects caused by pituitary tumors vary, but all are bounded by the midline. It is often associated with hypogonadism, impotence, amenorrhea, lactation, chill and weakness. Endocrine hormone measurement can help in the differential diagnosis, while retrobulbar optic neuritis is mostly related to infection, often accompanied by painful eye rotation and deep orbital pain, moderate pupil dilatation, dull or even absent light reflex, and central or dumbbell-shaped dark spot in the visual field. In addition, pituitary tumor may coexist with some ophthalmic diseases: patients complain of symptoms of glaucoma and fundus disease without intracranial symptoms and endocrine symptoms of pituitary tumor. In clinical work, detailed medical history should be taken, dynamic visual field examination should be performed, conceptual evaluation of visual field results should be avoided, and modern imaging and endocrine hormone examination should be fully utilized to prevent misdiagnosis. Although visual field examination is of great clinical significance, most of them cannot be detected in the early stage, and once they are detected, they are already in the late stage. When the pituitary tumor breaks through the saddle septum and pushes out the optic cross, it first produces a defect in the superior temporal quadrant, and then gradually expands to the inferior temporal, inferior and superior nasal areas. Clinically, because of the individual differences in the position of the optic cross and the pituitary gland, the early visual field may also appear as central dark spot, off-center dark spot or bundle dark spot. When patients are first diagnosed, although the receiving physicians consider to exclude the possibility of intracranial occupying lesions, they blindly and purposelessly perform cranial CT examinations instead of targeted thin-layer scans or intensified scans, so that some lesions with little difference in density or isointensity and some small lesions are not easily detected, giving physicians and patients the feeling that intracranial lesions are no longer considered, which causes long-term delay in treatment.
In conclusion, the lack of understanding of clinical manifestations of pituitary tumors, low vigilance, narrow knowledge, and lack of differential diagnosis ability due to the limitation of specialties, only give the diagnosis of symptoms, many tumor tissues can produce many kinds of ectopic hormones and appear corresponding symptoms without the performance of the primary foci, meanwhile, not enough attention is paid to endocrine examination, and the etiology is not carefully investigated, which are the reasons of misdiagnosis. Therefore, we should take a comprehensive medical history, examine the body carefully, strictly follow the clinical diagnostic procedures, never miss any suspicion, make comprehensive analysis, and make full use of imaging and endocrinological examination to achieve early diagnosis and treatment, reduce complications, and improve the cure rate.
Clinically, to avoid misdiagnosis of “pituitary tumor”, first of all, we should take a detailed medical history and examine the body carefully, as hypothyroidism patients have more complaints and may have general discomfort, no obvious positive signs on physical examination, and no abnormalities in general routine examination, and symptomatic treatment is ineffective; while pituitary tumor patients with reduced hormone secretion generally have clinical symptoms only after 3/4 of their glands are destroyed. In contrast, patients with pituitary tumors have clinical symptoms, and it is rare to have a single hormone deficiency, and they may have hypothyroidism, but it is not as common as hypogonadism and growth hormone deficiency, and the symptoms are generally mild and progress slowly, and the symptoms can be significantly aggravated during stress. After surgery, hypopituitary hypofunction not only increases the economic burden and mental stress of patients, but also significantly decreases the quality of life, especially in patients with juvenile hypothyroidism, because of the long duration of the disease, the pituitary MRI can show a large adenoma, and there are often some pressure symptoms, such as headache and visual impairment. In order to avoid unnecessary surgery, we should pay more attention to the functional evaluation of pituitary gland, thyroid gland and other target glands, especially the detection of autoimmune antibodies TGAb and TPOAb.