Post Therapy Evaluation and Treatment of Hormone Deficiencies

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Imaging

After surgery for nonfunctioning pituitary adenomas, patients should be followed for recurrence or incomplete resection with MRI scanning. We recom-

Hormone

Table 2

Suggested Postoperative Treatment and Monitoring of Patients with Nonfunctioning Pituitary Tumors

Replacement Therapy Monitoring

Prolactin None

Thyroid hormone L-thyroxine

Cortisol

Hydrocortisone or equivalent

Gonadal Estrogen/progestin hormones (premenopausal women);

testosterone (men) Growth hormone GH

Antidiuretic hormone dDAVP

None

Check free T4 every 6-8 wk until mid-normal free-T4 level achieved; then check free T4 yearly (TSH not useful) Biochemical testing not helpful for dose adjustment; avoid long-acting glucocorticoids Safety monitoring on a yearly basis

IGF-1 levels; ? Measures of body composition Clinical; Na levels mend postponing the first postoperative MRI until 4-6 mo after surgery, since earlier MRI does not adequately assess the extent of tumor resection (33). After a postoperative baseline has been established, MRI can be repeated every year for 3-5 years, and then less frequently if the tumor size is stable.

Endocrinology

Patients should also have a thorough endocrine evaluation, with treatment of any hormone deficiencies. This includes patients who were diagnosed with preoperative hormone deficiencies, because they can sometimes be reversed by the surgery (34,35). Our recommended evaluation is similar to that discussed earlier under "Endocrine Assessment" for preoperative patients, with a few exceptions (see Table 1). In patients who have postoperative pituitary hormone deficiencies, recommended endocrine treatment and monitoring strategies are listed in Table 2.

Prolactin

No postoperative testing for PRL is needed in patients who do not have prolactinomas.

Thyroid Hormones

A free-T4 level should be measured at least 6 wk after surgery, and L-thyroxine therapy started if the free-T4 level is low. The goal of L-thyroxine therapy is a mid-normal free-T4 level, and TSH levels are not helpful. Measuring free-T4 levels before 6 wk postoperatively is not helpful, because insufficient time has elapsed to assess the thyroid axis. Thyrotropin-releasing hormone (TRH) stimulation tests are not indicated. If L-thyroxine is started, repeated free-T4 levels should be measured every 6-8 wk until a mid-normal level is achieved. After this, the free-T4 level should be repeated yearly for a stable patient.

Adrenal Axis

Patients are usually sent home after pituitary surgery on replacement doses of hydrocortisone (15-30 mg/d according to protocol) or its equivalent to prevent symptomatic hypoadrenalism in case of pituitary damage. Higher doses or longer acting glucocorticoids are inappropriate, because they will lead to adrenal suppression.

Six weeks after surgery, patients should be instructed to withold their hydrocortisone dose on the day of testing, and a short ACTH stimulation test should be performed. Waiting 6 wk means that the adrenal glands will atrophy if there is ACTH deficiency, and an ACTH stimulation test will show a blunted cortisol response. In the past, high-dose ACTH (250 ^g) was used in this test, but recent publications suggest that low-dose (1 ^g) tests are more accurate in diagnosing ACTH deficiency (36). A cortisol response of <18 ^g/dL (500 nmol/L) 30 or 60 min after injection of 1 ^g of ACTH is consistent with ACTH deficiency, and the patient needs hydrocortisone replacement therapy. We tailor the amount of hydrocortisone to the patient's size and degree of ACTH deficiency. Smaller patients and those with mildly blunted ACTH stimulation tests do not always need traditional full dose (15-30 mg/d) hydrocortisone replacement.

Once a patient has been started on hydrocortisone, blood or urine tests are not particularly helpful in assessing dose adequacy, and clinical judgment is key to adjusting hydrocortisone doses to avoid symptoms of hypoadrenalism or exogenous Cushing's syndrome.

Gonadal Hormones

Postoperatively, loss of menses in a premenopausal woman is diagnostic of hypogonadism, and no further biochemical evaluation is needed. Young hypogonadal women require estrogen replacement therapy (oral contraceptives or equivalent therapy) to maintain well-being and bone mass.

Postmenopausal women with pituitary adenomas do not need an evaluation for gonadal deficiency, and decisions regarding estrogen replacement therapy are independent of the presence of tumor.

Men should have a testosterone level measured 6 wk after surgery. If the testosterone level is low, testosterone therapy should be initiated to maintain sexual function, body composition, and bone mass. There are four ways to administer testosterone therapy to hypogonadal men: (1) intramuscular injections every 2-3 wk, (2) daily transdermal patch, (3) daily testosterone gel, and

(4) in Europe some patients are given 2 or 3 200-mg pellets inserted subcutane-ously every 3-6 mo. Each delivery system has advantages and disadvantages, and the type of testosterone therapy should be individualized for each patient.

Once a patient is taking testosterone, yearly monitoring should be done for blood pressure, hemoglobin levels, lipid levels, and prostate disease, but testosterone levels do not need to be measured unless there is a clinical problem with efficacy. In the past, GnRH tests were used to evaluate patients with pituitary tumors and suspected gonadotropin deficiency, but this test does not add any useful information to the clinical evaluation and basal serum hormone levels.

In younger patients with pituitary tumors who desire fertility, hypogonadism is a more serious problem, because fertility is more difficult to achieve than sex steroid replacement. When fertility is required, such patients will need injections of exogenous gonadotropins, which have varied success in inducing fertility. A careful discussion should occur preoperatively with patients who desire future fertility to determine the extent of surgery and to review the options for preop-erative sperm retrieval and storage.

Growth Hormone

Until recently, adults with pituitary tumors were not evaluated for GH deficiency. However, numerous reports now provide convincing evidence that adults with GH deficiency have health consequences owing to lack of GH, including decreased well-being, changes in body composition and strength, adverse effects on lipids, and bone loss (37,38; and see Chapter 12). For that reason, many patients are now evaluated and treated for GH deficiency. However, the long-term consequences of treating patients with GH, sometimes for decades, are not known. For that reason, we individualize the decision to evaluate for GH deficiency after careful discussion with the patient.

Once the decision is made to evaluate the patient's GH axis, a stimulation test must be done, because basal GH or IGF-1 levels are not usually diagnostic. The most sensitive stimulation test for GH deficiency is an insulin tolerance test, in which subjects are rendered hypoglycemic with an insulin injection and the GH response is measured. However, this is a cumbersome test and is not recommended in older patients or those with cardiac disease or seizures. There is no consensus as to an acceptable alternative test, although a recent direct comparison of five commonly used tests (including the insulin tolerance test) suggests that a combination of arginine and growth hormone-releasing hormone (GHRH) provides the greatest reliability (38,39).

If a patient elects to begin GH therapy, the initial dose should be low to avoid side effects that are common when starting GH. The dose is then gradually increased based on IGF-1 levels, so as to reach a mid- to high-normal level for the patient's age. The optimal monitoring tests for a patient on GH are not standardized but can include measures of body composition, lipids, and bone density in addition to the IGF-1 levels.

Antidiuretic Hormone

Some patients will develop diabetes insipidus within a few days of surgery resulting from surgical damage and will require either temporary or permanent therapy with 1-deamino-D-arginine vasopression (dDAVP, a V2-receptor-selec-tive vasopression agonist).

In most cases, these patients have significant polyuria, polydipsia, and hypernatremia if they are denied access to free water. Aside from these patients, who are, fortunately, uncommon in expert surgical centers, we do not routinely evaluate or treat patients for diabetes insipidus (see Chaper 12).

If a patient complains of polyuria or significant nocturia after surgery, we usually begin with a simple 24-h urine collection for volume. If the 24-h volume is normal or high-normal, we do not pursue the evaluation. If the volume is high, the patient may need a water deprivation test to prove the presence of diabetes insipidus. Patients who do require dDAVP can be monitored clinically and with occasional serum sodium measurements.

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