1. Clinical manifestations and endocrine diagnosis of pituitary adenoma
1.1. Pituitary prolactin adenoma (PRL adenoma)
It is the most common pituitary functional adenoma, accounting for about 40-60 of pituitary adenomas, mostly seen in 20-30 years old.
(1) Female prolactin adenoma: It manifests as a typical triad of amenorrhea, lactation, and infertility.
(1) Amenorrhea: about 90. manifests as reduced, irregular or regular but low menstrual flow and amenorrhea.
(2) Lactation: Most patients have spontaneous milk-white fluid overflowing from the nipple, and some patients have it when squeezing the breast.
(3) Infertility: It accounts for about 63 and is one of the most common causes of infertility.
(2) Male prolactin adenoma: It is not uncommon. Because of the insidious clinical symptoms and easy to ignore endocrine symptoms, it does not attract enough attention from patients or is often seen in male departments, and is often diagnosed at an advanced stage. Early symptoms are mostly low libido, impotence, premature ejaculation, thinning hair, small testicles, etc. Headache, visual acuity and visual field disorders appear in the late stage.
Endocrinological examination: normal PRL≤20ug/ml. plasma PRL value >20ug/ml is hyperprolactinemia, if PRL>200ug/ml, it has obvious clinical significance.
1.2. Pituitary growth hormone adenoma (GH adenoma)
GH adenomas account for 20-30% of pituitary adenomas. If they occur before puberty, they appear as gigantism, and if they occur in adulthood, they appear as acromegaly. Acromegaly is characterized by enlarged head and jaw, high eyebrows, thickened nose and lips, enlarged hands and feet, thick skin, enlarged internal organs, bone and joint lesions, sleep apnea syndrome, etc. It is also associated with diabetes, hypertension, cardiovascular diseases, respiratory diseases, metabolic disorders and malignant tumors such as colon cancer. When the tumor increases in size, headache, visual field disorder and even increased intracranial pressure may occur.
Endocrine examination: normal plasma GH<5ug/L, if plasma GH>10ug/L, it is clinically significant. IGF-1 is often increased (exceeding the reference value of the same age and sex range). Also to be judged by whether serum GH levels are suppressed to normal after glucose loading.
1.3. pituitary adrenocorticotropic hormone adenoma (ACTH adenoma)
It is common in 20~40 years old, more in women than men. Clinical manifestations are centripetal obesity, acne, hypertrichosis, polycythemia face, purple lines, full moon face, buffalo back, hypertension, osteoporosis, etc. Men can present with hypogonadism, and women can present with menstrual disorders and infertility. Some patients develop superficial fungal infections, respiratory infections,, psychiatric abnormalities, metabolic disorders, etc.
Endocrinological examination: blood ACTH <80 pg/ml (normal value), if blood and urine cortisol exceeds normal value, pituitary ACTH adenoma can be diagnosed and differentiated from adrenal tumor and ectopic ACTH adenoma by dexamethasone suppression test.
1.4. pituitary thyrotropic adenoma (TSH adenoma)
TSH adenomas account for less than 1 of pituitary adenomas. Clinical manifestations are symptoms of hyperthyroidism: panic, fear of heat, trembling of limbs, irritability, and weight loss, etc., accompanied by symptoms of saddle occupancy: headache and visual field disturbance.
Endocrinological features: serum thyroid hormone levels and TSH levels are elevated simultaneously. In 80 TSH adenomas, the a-subunit production of glycoprotein hormone is increased and the ratio of a-subunit to TSH can be measured to be greater than 1, which is an auxiliary evidence for the diagnosis of thyrotropin cell adenoma.
1.5. non-functioning pituitary adenomas
Pituitary adenomas account for approximately 25 of all pituitary adenomas, including gonadotropin adenomas, naked cell adenomas, and eosinophilic adenomas. There are signs of hypopituitarism: weakness, coldness, excessive sweating, loss of libido, impotence and premature ejaculation in men, with symptoms of saddle area compression: hypotony and visual field defects.
Some patients can develop pituitary stroke, accounting for about 1 to 2 , with clinical manifestations such as sudden and severe headache, vomiting, sharp loss of vision, diplopia, and ocular muscle paralysis. This is due to the rupture of the abnormal vessels in the pituitary tumor and the superior pituitary artery immediately adjacent to the saddle septum under pressure. The rapid expansion of the tumor caused by the dramatic increase in intra-tumoral pressure and volume results in mechanical compression of the structures within the cavernous sinus. This may result in partial or total, temporary or permanent pituitary hypoplasia. Uveitis as a complication of pituitary stroke is very rare and is related to the fact that the posterior pituitary gland has its own blood supply and usually avoids damage.
Endocrinological examination: there are low levels of functional pituitary hormones and some patients can develop moderate hyperprolactinemia due to compression of the pituitary stalk.
2.Imaging diagnosis of pituitary adenoma
Imaging is an important tool to evaluate pituitary adenomas and surrounding structures. MRI is currently the imaging method of choice for pituitary lesions and is superior to CT in showing the outline of pituitary lesions and determining the relationship between the tumor and the soft tissue structures adjacent to the saddle.
CT of the pterygoid saddle mainly suggests changes in bone, and in the case of microadenoma, an isointense or slightly hypointense area with increased pituitary height and limited elevation of the superior pituitary margin. On enhancement scans, the pituitary gland enhances before the tumor. For macroadenoma, the CT scan shows enlargement of the pterygoid saddle, rounded isointense tissue in the saddle and suprasaddle pool with clear boundary, and low-density area inside the tumor with different degrees of enhancement.
3.Differential diagnosis of pituitary adenoma
Pituitary adenoma should be differentiated from other tumors and non-neoplastic diseases in the saddle area.
3.1. Differentiation of intra-saddle and supra-saddle tumors
①Craniopharyngioma
Craniopharyngioma is classified into enamel cell type and squamous papillary type according to the pathology. The enamel cell type can be seen in children and adults, while the squamous papillary type is only seen in adults. The typical presentation is pituitary endocrine hypoplasia with developmental arrest, dwarfism and, in about 1/3 of cases, uveitis. The visual field is monocular or bilateral temporal hemianopsia, and the optic papillae are either primary or secondary atrophy. The cranial CT shows normal or pelvic enlargement of the pterygoid saddle, low density cystic occupancy in the saddle, shell-like calcification of the cyst wall in 2/3 patients, shell-like calcification is valuable for confirming the diagnosis. MRI shows cystic masses in the supra- and intra-saddle, 70%-90% are cystic, the cyst wall is circularly reinforced, mostly calcified, either long T1 and long T2, or short T1 and short T2.
②Saddle node meningioma
CT scan shows a uniform, well-defined, high-density image with saddle nodule as the base, the base is wider and has more obvious enhancement, the butterfly saddle is not enlarged and there is no bone destruction. MRI of the head shows a slightly long T1 or iso-T1, slightly long T2 lesion at the saddle nodes, often intersecting with the dural surface at an obtuse angle, with obvious enhancement, and the tumor is located in the suprasellar pool, with normal pituitary structure and characteristic meningeal tail sign.
(3) Chordoma
The clinical manifestations are headache, hypopituitarism and cranial nerve disorder, without symptoms of hyperpituitarism. It usually occurs in the midline of the skull base and develops in the upper and lower saddle and intracranial area with the slope as the center. Cranial CT shows extensive destruction of bone in the midline of the skull base, including the pterygoid saddle, pterygoid sinus and slope. MRI of the skull showed that the slope pattern disappeared, and the lesion signal was heterogeneous and irregular in shape, with the center of the skull base midline area compressing the surrounding structures, which could have different degrees of enhancement.
Epithelioid cyst
Epithelioid cysts mostly occur in the skull base and saddle side, and epithelioid cysts in the saddle area account for 3% of all cases. Generally, there are no endocrine symptoms, and in rare cases, there are sexual dysfunction, polydipsia and polyuria. Due to long-term invasion of the skull base, it can also be accompanied by multiple groups of cranial nerve damage symptoms. CT scan shows hypointense shadow with CT value between 2 and 12, which is lower than cerebrospinal fluid value.
⑤ Optic crossbrain tumor
The main symptoms are visual impairment, visual field narrowing and optic papillary edema, and also anterior pituitary dysfunction. Cranial MRI shows that the tumor is closely related to the optic chiasm, with iso-T1 or long T1, iso-T2 or long T2 signals, and normal or compressed pituitary structures.
(6) Ectopic pineal tumor
Ectopic germ cell tumors occur in children and adolescents and manifest as anterior and posterior pituitary lobe dysfunction, with the latter lobe dysfunction being the most prominent symptom, and uveitis is often the only first symptom. The cranial CT showed a round, well-defined, mixed-density or high-density suprasellar occupancy with homogeneous and consistent enhancement, and the butterfly saddle was mostly normal in size and shape. The cranial MRI showed long T1 and long T2 signal lesions.
(7) Nerve sheath tumor
If the tumor is large, it may invade the saddle, and the clinical manifestation is pain and numbness in the trigeminal nerve distribution area. The clinical manifestation is pain and numbness in the trigeminal nerve distribution area. CT scan of the head shows a round or dumbbell-shaped occupancy with clear boundary, slightly high density and obvious changes of enhancement.
3.2. Identification of intra-saddle supra-saddle non-neoplastic disease
(1) Vacuolation saddle
It is congenital because of congenital septal hypoplasia or absence of such, and secondary because of hydrocephalus, pituitary lymphitis, degenerative degeneration of pituitary gland, pituitary tumor surgery or radiotherapy. The clinical manifestations include migraine, visual field disturbance, cerebrospinal fluid nasal leakage, hypopituitarism, hyperprolactinemia, and uremia, etc. CT scan shows hypodense areas in the saddle, enlarged or normal pterygoid saddle, symmetrical compression and flattening of the pituitary gland. MRI shows cerebrospinal fluid signal shadow and saddle septal dysplasia in the pterygoid saddle. The pituitary stalk is prolonged and the optic nerve is elevated.
②Lacrimal cyst
In the second week of embryonic period, a blind pouch called Rathke’s pouch protrudes from the roof of the primitive oral cavity, and in normal individuals, there are small cysts of 1-5 mm in diameter between the anterior and posterior lobes of the pituitary gland, which are the embryonic remnants of Rathke’s pouch. MRI scan shows equal or high signal on T1-weighted image and different signal on T2-weighted image.
(iii) Pituitary abscess
CT scan shows enlargement of the pterygoid saddle and low-density cystic lesions in the saddle, with substantial or circumferential enhancement after enhancement. There is relatively obvious enhancement of the sac wall.
Intracranial aneurysm
It is rare, occasionally seen in middle-aged and elderly people, usually in the paracranial or suprasellar area, with clinical manifestations of sudden headache, associated with vision loss, and paralysis of one side of the motor nerve. The degree of visual impairment is not proportional to the size of the lesion. MRI shows that the lesion has a blood flow effect, the tumor wall is often calcified, the area with blood inside the tumor is significantly strengthened, the lesion is connected with the arterial ring of the base of the brain, cerebral angiography (DSA) can make a clear diagnosis, but we should be alert to pituitary adenoma combined with aneurysm.
⑤ Traffic hydrocephalus
Due to the general dilatation of the ventricles, it can extend into the pterygoid saddle causing enlargement of the pterygoid saddle. Clinical manifestations may include visual field impairment, and a few patients also have endocrine symptoms such as amenorrhea and obesity. CT and MRI of the head show symmetrical enlargement of the ventricles, and the enlargement of the third ventricle extends into the saddle.
(6) Pituitary inflammation
The clinical manifestations include headache, nausea, vomiting, fever, neck stiffness, and anterior and posterior pituitary lobe dysfunction. MRI can clearly show thickening of the pituitary stalk, which can extend to the base of the hypothalamus with different degrees of enhancement.
(7) Visual field impairment needs to be differentiated from retinopathy caused by diabetes mellitus and hypertensive atherosclerosis.
(8) The symptoms of hypo or hyper endocrine function need to be differentiated from pregnancy and physiological menstruation.