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Biomedical subjects

G Dickstein

Publications and source records attributed to G Dickstein.

At least 19 recordsLinked to original sources

Low-dose adrenocorticotropin test reveals impaired adrenal function in patients taking inhaled corticosteroids.

The aim of the present study was to examine the use of low-dose ACTH-(1-24) stimulation for assessment of adrenal function and the detection of mild adrenal insufficiency. The criteria for normal response to ACTH-(1-24) are a peak cortisol level of more than 500 nmol/L (18.1 micrograms/dL) and an increment of the cortisol level above the basal one of more than 200 nmol/L (7.2 micrograms/dL). These criteria were satisfied by 32 of 33 healthy children and adults subjected to an ACTH-(1-24) dose 500 times lower (0.5 micrograms/1.73 m2) than the dose of 250 micrograms in the standard test. At 20 min, the peak cortisol level was the same in the low-dose test [(621 +/- 28 nmol/L) (22.5 +/- 1.0 microgram/dL)] as in the standard ACTH test [(654 +/- 31 nmol/L) (23.7 +/- 1.1 microgram/dL)]. Of 46 asthmatic patients who had been treated with inhaled beclomethasone dipropionate (482 +/- 42 micrograms/m2 daily; n = 32) or budesonide (507 +/- 62 micrograms/m2 daily; n = 14) for over 6 months, 16 (35%) failed to reach a cortisol peak of more than 500 nmol/L (18.1 micrograms/dL) following stimulation with 0.5 micrograms ACTH-(1-24)/1.73 m2. Of these, 11 (24%) showed a cortisol increment of less than 200 nmol/L (7.2 micrograms/dL). These 16 patients, showing insufficient response to low-dose ACTH-(1-24), also had a significantly lower (P < 0.01) mean 24-h urinary free cortisol excretion [(71 +/- 10 nmol/m2.24 h) (25.7 +/- 3.6 micrograms/m2.24 h)] than patients who responded normally [(118 +/- 11 nmol/m2.24 h) (42.8 +/- 4.0 micrograms/m2.24 h). Nonetheless, all but one of the poor responders to a 0.5 microgram ACTH showed normal stimulation with the standard 250 micrograms ACTH test. Therefore, it appears that a low-dose ACTH test is capable of revealing mild adrenal insufficiency, which is not detected by the standard high-dose ACTH test.

Administration, Inhalation

Toxic Graves' disease with thyroid hemiagenesis: diagnosis using thyroid-stimulating immunoglobulin measurements.

Two patients with hemiagenesis of the thyroid gland experienced thyrotoxicosis. They constituted 1.1% of our clinic's total population of 178 thyrotoxic patients treated in the years 1986-1990 and 1.7% of 120 patients with thyrotoxic Graves' disease encountered during that period. The diagnosis was made on the basis of unilateral homogeneous 99mTcO4 uptake on thyroid scan, no change in the scan after both cessation of propylthiouracil (PTU) treatment for 4 days and TSH stimulation test, and high thyroid-stimulating immunoglobulin (TSI) levels. Both patients went into remission after PTU treatment, and TSI levels returned to normal. The diagnosis of toxic Graves' disease with thyroid hemiagenesis was, therefore, made. This combination is rare but important to recognize because treatment as well as prognosis might be different from that of toxic adenoma.

Adult

Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test.

Adrenal response to iv administration of 1-24 ACTH (250 micrograms) was examined in normal volunteers under various conditions. The effect of basal cortisol levels was examined by performing the tests at 0800 h with and without pretreatment with dexamethasone. The effect of time of day was evaluated by performing the tests at 0800 h and at 1600 h, eliminating possible basal cortisol influence by pretreatment with dexamethasone. In the first set of tests, despite significantly different baseline levels, 30-min cortisol levels were not different (618 +/- 50 vs. 590 +/- 52 nmol/L). Afternoon cortisol levels in response to ACTH were found to be significantly higher than morning levels at 5 min (254 +/- 50 vs. 144 +/- 36 nmol/L, p less than 0.01) and at 15 min (541 +/- 61 vs. 433 +/- 52 nmol/L, p less than 0.02). This difference in response was no longer notable at 30 min (629 +/- 52 and 591 +/- 52 nmol/L). We tried also to determine the lowest ACTH dose which will elicit a maximal cortisol response. No difference was found in cortisol levels at 30 and 60 min in response to 250 and 5 micrograms 1-24 ACTH. Using 1 micrograms ACTH, the 30-min response did not differ from that to 250 micrograms (704 +/- 72 vs. 718 +/- 55 nmol/L, respectively). However, the 60-min response to 1 microgram was significantly lower (549 +/- 61 vs. 842 +/- 110 nmol/L, p less than 0.01). Using this low dose ACTH test (1 microgram, measuring 30-min cortisol level), we were able to develop a much more sensitive ACTH test, which enabled us to differentiate a subgroup of patients on long-term steroid treatment who responded normally to the regular 250 micrograms test, but had a reduced response to 1 microgram. The stability of 1-24 ACTH in saline solution, kept at 4 C, was checked. ACTH was found to be fully stable after 2 hs in a concentration of 5 micrograms/ml in glass tube and 0.5 micrograms/ml in plastic tube. It was also found to be fully stable, both immunologically and biologically, for 4 months, under these conditions. We conclude that the 30-min cortisol response to ACTH is constant, unrelated to basal cortisol level or time of day. It is therefore the best criterion for measuring adrenal response in the short ACTH test. The higher afternoon responses at 5 and 15 min suggest greater adrenal sensitivity in the afternoon, but further studies are needed to clarify this issue.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Spontaneous remission in Cushing's disease.

Four patients with proved Cushing's disease underwent spontaneous clinical and biochemical remission. They were part of an 11-patient group treated with methods that allowed spontaneous remission to be observed. Each patient was treated differently, one each with metyrapone tartrate, ketoconazole, bilateral adrenalectomy and adrenal autotransplantation, and no treatment. Spontaneous remission occurred 9 months to 5 years after diagnosis as evidenced by restoration of normal adrenal function occurring symptomatically in two patients and advent to hypoadrenalism with addisonian crisis in the two others. We conclude that spontaneous remission in Cushing's disease may not be a rare entity, although its actual incidence has yet to be established.

Adolescent

Factors predicting the outcome of varicocele repair for subfertility: the value of the luteinizing hormone-releasing hormone test.

The mechanism by which varicocele caused infertility is not yet clear. Endocrine factors have been suggested to explain impaired spermatogenesis in patients with varicocele. We conducted a prospective study on testosterone and gonadotropin levels and their response to the luteinizing hormone-releasing hormone test to determine the possible role of a hormonal defect in subfertility. Luteinizing hormone-releasing hormone tests were performed on 11 subfertile men with varicocele preoperatively and 3 months postoperatively. The differences in the luteinizing hormone response were statistically significant. The maximal luteinizing hormone levels also were significantly lower in patients whose spermiogram changed postoperatively. No significant changes were noted in testosterone and other gonadotropin levels postoperatively. A prognostic correlation between the change in response of luteinizing hormone to luteinizing hormone-releasing hormone (preoperatively and postoperatively) and improvement in fertility (pregnancy success) was found. We suggest that the luteinizing hormone-releasing hormone test should be considered to estimate the hormonal derangement and also the prognosis of an operation in subfertile men with varicocele.

Adult

Inflammatory bowel disease: specific concerns in the elderly.

Despite recent improvements in our knowledge concerning IBD in the elderly, much is still unknown. Fundamental issues which remain unresolved are: the true frequency of disease onset in old age; the natural history and location of disease; the response of these patients to medical therapy; the indications for surgery; the incidence of postoperative recurrence; and the incidence of cancer complicating existing disease. Nevertheless, reasonably successful treatment options are available to many elderly IBD patients, given that an alert and careful diagnostician identifies the problem.

Aged

Primary therapy for Cushing's disease with metyrapone.

A 13-year-old boy was diagnosed as suffering from pituitary-dependent Cushing's syndrome. He was treated with 2.0 g of metyrapone daily as the sole treatment for four years. All clinical and biochemical stigmata of Cushing's disease disappeared within a few months. The patient grew 23.0 cm in four years and regained normal health. No significant side effects of metyrapone were noticed. Administering the medication at 2 PM and 8 PM allowed higher cortisol levels in the morning and noon hours than in the evening and night, approximating the normal diurnal variation in cortisol production. We conclude that metyrapone may be considered the sole treatment in patients with Cushing's disease.

Adolescent

Single-dose metyrapone test at 06.00 h: an accurate method for assessment of pituitary-adrenal reserve.

One dose of metyrapone (1.5g) administered at 06.00 h, with subsequent measurement of 11-deoxycortisol and 17-hydroxycorticosteroid (17-OHCS) levels in plasma at 12.00 and 14.00 h, allowed accurate assessment of the pituitary-adrenal reserve. Normal response was defined as achieving a serum 17-OHCS level of more than 10.0 micrograms/100 ml and a 11-deoxycortisol level of more than 6.0 micrograms/100 ml at either 12.00 or 14.00 h. These criteria are based on a group of 18 persons with normal pituitary-adrenal axis, and 86 additional cases responded in this normal range. In this group of 104 subjects, 11-deoxycortisol levels rose to 9.2 +/- 3.5 micrograms/100 ml at noon and 17-OHCS levels to 15.4 +/- 4.7 micrograms/100 ml at 14.00 h. Post-metyrapone 17-OHCS levels were significantly higher than normal cortisol levels at these times (P less than 0.001) and than those observed at 08.00 h on the day of the test, demonstrating stimulation of adrenal corticoid production in addition to blockade of cortisol production by metyrapone. Thirty-one patients found to suffer from secondary adrenal failure showed impaired response. All these patients had limited pituitary-adrenal reserve, either proven by other pituitary-adrenal tests or implicated by severe pituitary disease.

17-Hydroxycorticosteroids

Hypothyroidism secondary to biologically inactive thyroid-stimulating hormone secretion by a pituitary chromophobe adenoma: recovery after removal of the tumor.

A 50-year-old man, suffering from a large pituitary adenoma and panhypopituitarism, was found to have severely elevated thyrotrophin (thyroid-stimulating hormone [TSH]) levels (greater than 20.2 microunits/mL). The thyroxine (T4) level was low (less than 3.0 micrograms/dL). Thyroid sodium iodide I 131 uptake was low (5% at 24 hours). A TSH test result was normal, with a 24-hour 131I uptake of 52% and a normal-looking thyroid gland on scintiscan. After surgical removal of the pituitary chromphobe adenoma, T4 levels returned to normal (6.8 micrograms/dL) and TSH levels improved substantially (9.0 microunits/mL). Findings from repeated 131I uptake tests were normal (22% at 24 hours). Other pituitary functions improved also. These results suggest that the patient had biologically inactive TSH produced by the tumor. Removal of the tumor probably enabled recovery of the active TSH with the return of normal thyroid uptake and T4 production. Whenever hypothyroidism and high levels of TSH coexist with pituitary dysfunction, a TSH test is needed to distinguish between primary hypothyroidism and hypothyroidism secondary to biologic inactive TSH.

Adenoma, Chromophobe

Bromocriptine-induced pregnancy in an acromegalic patient.

A 30-year-old acromegalic woman with amenorrhea and elevated growth hormone and prolactin levels was treated with bromocriptine. Growth hormone levels remained elevated, while prolactin levels decreased to normal. Forty days after initiating treatment the patient menstruated and conceived shortly afterward. The uneventful pregnancy terminated in delivery of a normal baby, who has been developing normally since. No changes in the size of the sella turcica or the visual field were noted during pregnancy and up to one year after delivery. Resumption of ovulatory menses is possible when treating acromegalic women with bromocriptine. Hyperprolactinemia rather than elevated growth hormone levels or reduced gonadotropins reserve is probably the cause for amenorrhea in some of the acromegalic patients.

Acromegaly

Complete remission of Cushing's disease by total bilateral adrenalectomy and adrenal autotransplantation.

A 15-yr-old girl was diagnosed as suffering from Cushing's disease. She was treated by bilateral adrenalectomy and autotransplantation of one third of each adrenal to the corresponding thigh. The adrenal that was embedded in the right satorius muscle started functioning after about 1 yr, as proven by significant differences in cortisol levels in both femoral veins (82.5 and 17.5 micrograms/100 ml). 19-[131I]Cholesterol scanning showed adrenal tissue in the right thigh, while no adrenal remnant was demonstrated. Eleven years after surgery, the patient is symptom free and does not require replacement therapy. We find that adrenal autotransplantation, which is a simple and nonrisky procedure, should be considered whenever bilateral adrenalectomy is chosen as a treatment for Cushing's disease.

17-Ketosteroids

Improved single-dose metyrapone test.

One dose of metyrapone (1.5 g) administered at 6 AM, with subsequent measurement of plasma ACTH, 11-deoxycortisol, or 17-hydroxycorticosteroids (17-OHCS) (cortisol + 11-deoxycortisol) at noon and 2 PM allowed an accurate assessment of the pituitary-adrenal reserve. Eighteen subjects with a normal pituitary-adrenal reserve were studied before and after the administration of this single metyrapone dose. By noon, plasma ACTH rose from a premedication value of 39 +/- 22 (SD) to 193 +/- 104 pg/ml and 11-deoxycortisol, from 0.0 +/- 0.3 (SD) to 9.0 +/- 2.7 microgram/dl. By 2 PM, plasma 17-OHCS had increased from a premedication value of 5.0 +/- 1.5 (SD) to 16.0 +/- 1.8 microgram/dl. The differences between pre- and postmedication values were statistically significant for all indices measured (P less than 0.001). No overlap was found between values before and after metyrapone. This protocol eliminates the need for metyrapone administration every 4 h over a 24-h period. It offers the advantage of low dose and low toxicity. The integrity of the pituitary-adrenal axis can be demonstrated by measuring either plasma ACTH and 11-deoxycortisol or even 17-OHCS 6 to 8 h after the administration of this single metyrapone dose.

17-Hydroxycorticosteroids

Complete remission of acromegaly with medical treatment.

A 40-year-old patient with a ten-year history of acromegaly had persistent disease despite prior treatment with conventional pituitary radiotherapy and two transsphenoidal hypophysectomies. Initial evaluation showed characteristic acromegalic features, hypertension, amenorrhea, inappropriate diaphoresis, and poorly controlled diabetes mellitus despite isophane insulin suspension daily. Growth-hormone levels were high and did not suppress with glucose load. Treatment with bromocriptine was associated with prompt improvement in glucose intolerance, with elimination of insulin requirement within 72 hours of institutions of this therapy. Blood pressure normalized; inappropriate diaphoresis disappeared. Within three months ovulatory menses were noted to resume for the first time in ten years. There was progressive improvement in the soft-tissue changes of acromegaly. The growth-hormone levels fell within three hours after the first dose of bromocryptine and remained suppressed throughout her six-month course of therapy.

Acromegaly

Bromocriptine and endocrine disorders.

Bromocriptine, a dopaminergic agonist, has been used to treat many endocrine disorders. In hyperprolactinemia associated with galactorrhea, amenorrhea, oligospermia, and impotence, bromocriptine reduces prolactin levels to normal and allows for satisfactory return of sexual and reproductive function in 90% of patients. In acromegaly, bromocriptine brings about subjective improvement in 75% of patients with reduction in growth-hormone levels to normal in 22% of patients. Bromocriptine has been used in premenstrual tension, functional infertility, Nelson's syndrome, and Cushing's disease with variable benefit. In low doses, side-effects are minimal. In higher doses, digital vasospasm and gastrointestinal bleeding have occurred. Although bromocriptine has been used in a wide variety of endocrine disorders, it appears to be most useful in treatment of male and female infertility associated with hyperprolactinemia.

Acromegaly