Examination for hypopituitarism

Hypopituitarism must be diagnosed before lifelong hormone replacement therapy can be given to the patient. Look for evidence of structural abnormalities of the pituitary gland and hormone deficiency. X-ray examination of the sella turcica and formal visual field measurement can detect tumors. High-resolution CT scan (with contrast agent if necessary) is the diagnostic technique of choice for diagnosing pituitary adenomas. If there is no condition for high-resolution CT scanning, multi-slice X-ray tomography of the sella turcica becomes a major diagnostic method. Cerebral angiography is only necessary if a dynamic CT scan indicates possible abnormality or aneurysm in the perisellar vessels. If modern neuroradiological diagnostic equipment is not available in the patient's area, a cone lateral X-ray of the sella turcica can still be a reasonable differential diagnosis for pituitary macroadenomas greater than 10 mm in diameter.

Once panhypopituitarism is suspected, first check for deficiencies of TSH and ACTH, because deficiencies of both hormones are potentially life-threatening.

In order to diagnose whether a patient has hypothyroidism, radioimmunoassay can be used to measure the levels of T4, T3 and TSH. All measured results should be classified as low, because elevated TSH levels mean that the thyroid abnormality is primary. Intravenous injection of 200 to 500 μg of thyroid-stimulating hormone-releasing hormone (Protirelin, a synthetic TRH) within 15 to 20 seconds can help in the differential diagnosis of patients with hypothalamic or pituitary gland dysfunction. Under normal circumstances, the TSH response to TRH can be observed to reach its peak level 30 minutes after injection. Delayed increases in plasma TSH levels may be seen in patients with hypothalamic disorders. Unfortunately, some patients with primary pituitary disease also have such an abnormal TSH response.

Evaluation of ACTH secretion begins with the collection of 24-hour urine specimens to measure urinary free cortisol and 17-OHCS. In hypopituitarism the levels of both substances should be reduced. Unfortunately, basal cortisol secretion is often normal, even in the presence of reduced ability to release ACTH in early or partial hypopituitarism. It can be seen that it is of more practical significance to evaluate the reserve capacity of ACTH secretion. If the adrenal cortex function is normal, there should be a significant increase in plasma cortisol (at least an increase of 7 μg/dL) after intravenous infusion of 0.25 mg cosyntropin within 15 to 30 seconds or 2 hours later. or reach levels above 20 μg/dL). In primary adrenal insufficiency (Addison's disease), the response to this stimulus is diminished. However, if ACTH deficiency persists for a long time, the cortisol response may also be diminished. Therefore, the most reliable method for evaluating ACTH (and also for evaluating GH and PRL) reserve capacity is the insulin resistance test. Inject 0.1u intravenously within 15 to 30 seconds. /kg body weight dose of regular insulin, and then take venous blood samples at 0 minutes (that is, before insulin injection) and 20, 30, 45, 60, and 90 minutes to measure GH, cortisol, and glucose. If the serum glucose level does not drop by more than 50% to a level below 40 mg/dL, the test should be repeated. For diabetic patients and the elderly diagnosed with severe panhypopituitarism, this test is dangerous: if there is ischemic heart disease or epilepsy, this test is contraindicated. Therefore, medical supervision is necessary when conducting this test. Usually only transient sweating, tachycardia, and nervousness occur during this test. Once the patient complains of palpitations, loss of consciousness, or seizure, the test should be stopped immediately and a 50% glucose solution should be injected intravenously.

An insulin resistance test alone cannot differentiate between primary (Addison's disease) and secondary (pituitary) adrenal insufficiency unless ACTH and cortisol are also measured. Unfortunately, it is still difficult to accurately measure plasma ACTH concentration.

During the metyrapone test, plasma cortisol levels will decrease because the 11-hydroxylation of the cortisol precursor is blocked by metyrapone. In normal humans, a decrease in cortisol levels will stimulate an increase in ACTH and lead to an increase in the production of cortisol precursors (especially 11-deoxycortisol), which are excreted in the urine in the form of 17-OHCS. Because the methotrexate test only measures the secretion of ACTH that is inhibited by steroids, stress responses that do not inhibit the secretion of ACTH (such as surgery) may cause the release of ACTH, even in those who do not respond to methotrexate. The same goes for patients. 24-hour urine samples were taken on two consecutive days and baseline levels of 17-OHCS were determined. On the third day, 750 mg (for children, 300 mg/m^2 body surface area) of methylpyrazofen was administered orally from 8 a.m., then once every 4 hours, 6 times per day, the total dose for adults is 4 ．5g. If on the last day of such treatment (i.e. day 4), or one day after such treatment, the urinary 17-OHCS does not double, or the plasma 11-deoxycortisol level does not exceed 10 μg/dL , it is abnormal. Dizziness and nausea often occur, but can be relieved by bed rest.

Because the absence of a response to methotrexate may indicate hypothalamic-pituitary insufficiency or adrenal failure, it is often helpful to perform an ACTH stimulation test on day 4.

Patients with adrenal insufficiency or hypopituitarism often have a reduced or absent response to methotrexate. But some people with hypothalamic or pituitary disease have normal responses. This reaction may also be abnormal in normal people with increased metabolism of methotrexate, patients with hyperthyroidism, some pregnant women, and patients taking phenytoin or estrogen.

Corticotropin-releasing hormone (CRH) test: The recently discovered and synthesized CRH provides a better method for measuring hypothalamic-pituitary-adrenal function than any of the previous tests; but now it Use remains within the scope of scientific research. Intravenous infusion of 1 μg/kg of CRH over 20 seconds appears to elicit maximal responses in both ACTH and cortisol. Plasma ACTH can increase within 2 minutes after CRH injection, and the first peak appears within 10 to 15 minutes. After the first peak, the concentration of ACTH decreased, but formed a second peak at the third hour: the increase in plasma cortisol was faster, starting 10 minutes after the injection, and continuing at 30 to 60 minutes. reaches the peak value.

Patients with primary adrenal insufficiency have a significantly enhanced response to CRH, probably because there is no immediate negative feedback inhibition by glucocorticoids when CRH acts on the pituitary gland. Patients with secondary adrenal insufficiency either have no response to ACTH, have a weak response (presumably due to primary pituitary ACTH deficiency), or have increased and prolonged response (presumably due to primary hypothalamic CRH). insufficient). Although there are now simpler and more direct methods for diagnosing primary adrenocortical insufficiency, further research may show that CRH is valuable in identifying secondary adrenal insufficiency as having a hypothalamic or pituitary cause.

In people with panhypopituitarism, PRL levels are not always reduced. In fact, high levels of PRL can also be seen in hypothalamic diseases if prolactin cells have escaped the inhibitory effects of dopamine.

The measurement of GH is only valuable if one of several stimulating stimuli is selected for stimulation and then measured again: because in individuals with reduced thyroid or adrenal function, the GH response is often abnormal. So this test should only be done after appropriate hormone replacement therapy. Insulin resistance testing is the most effective stimulus for GH release. The following GH release tests are less risky but less reliable: using arginine infusion (500 mg/kg intravenously over 30 minutes), oral levodopa (500 mg for adults, 10 mg/kg for children), sleep, Or 20 minutes of vigorous exercise. Clonidine (4 μg/kg orally) is another powerful stimulant of GH secretion and is likely to be used as a substitute for insulin. The side effects are only salivation and a slight decrease in blood pressure. Generally speaking, as long as the GH value is >10ng/ml, or the response value after one stimulation is >5ng/ml, it is enough to rule out the existence of GH deficiency. The elevated value of GH is <5ng/ml, or the level is <10mg/ml. Such phenomena are difficult to explain. Every normal reaction occurs randomly, and all provocative tests of GH secretion occasionally produce erroneous results. Because no test is 100% effective in eliciting GH release, at least 2 different tests should be performed when no GH response occurs. Generally speaking, the time for the GH level to reach the bee value is as follows: 30 to 90 minutes after the administration of insulin, 30 to 90 minutes after the start of arginine infusion, 30 to 120 minutes after the administration of levodopa, and the administration of clonidine after falling asleep 60 to 120 minutes after exercise, 20 minutes after intense activity.

Whether exogenous GRH is useful for understanding GH secretion has not yet been determined. Intravenous injection of 1 μg/kg GRH within 15 to 30 seconds can cause extreme release of GH, but the amount of release varies greatly, typically reaching a peak 60 minutes after GRH injection. If the GH response to GRH is absent or only slightly enhanced, some individuals can be identified as having GH deficiency: however, whether this response pattern can differentiate primary hypothalamic disease from pituitary disease has not been elucidated.

Measurement of basal serum LH and FSH levels is extremely valuable for determining hypopituitarism in postmenopausal women who do not use exogenous estrogen. Under normal circumstances, the concentration of gonadotropin in their circulating blood is relatively high (>40mlU/ml). But for other patients, measuring basal levels of LH and FSH is of little value. Although gonadotropin levels are low in panhypopituitarism, there is overlap with the normal ranges of LH and FSH. If 100 μg of gonadotropin-releasing factor hydrochloride (i.e., synthetic GnRH) is injected intravenously, the levels of LH and FSH should increase, with the peak value of LH occurring at approximately 30 minutes after injection and the peak value of FSH occurring at 40 minutes after injection. hour. However, when the hypothalamus and pituitary gland are dysfunctional, the response to GnRH can also be normal, weakened or absent. The normal increase in LH and FSH responses to GnRH is variable.

Furthermore, the use of exogenous GnRH does not help differentiate primary hypothalamic disease from primary pituitary disease.

The most effective method for evaluating pituitary function is to measure the pituitary reserves of several hormones at the same time. 0.1u of islet cord can be injected intravenously within 15 to 30 seconds. /kg regular insulin), TRH (200μg) and GnRH (100μg). Levels of glucose, cortisol, GH, TSH, prolactin, LH, FSH, and ACTH were measured at regular intervals over the next 180 minutes. Another method is to inject insulin alone first, and then 120 minutes later inject TRH and GnRH simultaneously. Some people advocate that TRH and GnRH should be injected simultaneously with intravenous injection of GRH (1 μg/kg) and CRH (1 μg/kg), and there is no need to use the insulin cord as part of the composite test of anterior pituitary function. In short, the practical value of these commercially available releasing hormones for testing pituitary function remains to be determined. Regardless, the normal reaction is the same as described in the past.