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C M Feek

Publications and source records attributed to C M Feek.

At least 37 records · Page 2Linked to original sources

The adrenal gland and progesterone stimulates testicular steroidogenesis in the rat in vivo.

Administration of pharmacological doses of glucocorticoid to male rats in vivo suppresses adrenal steroidogenesis and inhibits testicular steroidogenesis by inhibiting the anterior pituitary secretion of LH. In contrast, administration of ACTH to these pharmacologically-suppressed rats stimulates the adrenal secretion of progesterone and testicular steroidogenesis. The mechanism by which ACTH increases testicular steroidogenesis is dependent on the presence of the adrenal gland and is reproduced by the administration of progesterone. The conclusion from these data is that the adrenal gland has an important role in generating external signals that modulate the hypothalamic-pituitary-gonadal axis in male rats. The adrenal secretion of glucocorticoid acts as a negative signal to testicular steroidogenesis whereas progesterone acts as a positive signal. The adrenal secretion of progesterone and its conversion to testosterone by steroidogenic enzymes in the cytoplasm of the Leydig cell may provide an alternative pathway for testosterone biosynthesis and may account for the increased plasma testosterone levels during the acute phase of stress and mating.

Adrenalectomy↗

Adrenalectomy does not influence basal secretion of testosterone in rat in vivo.

We have studied the effect of adrenalectomy on the testicular secretion of testosterone in the rat. In the acute period following adrenalectomy plasma testosterone levels were reduced but this was no different from those levels in appropriate sham-operated controls. This reduction in plasma testosterone levels is probably a result of direct effects of anaesthesia and surgical stress. Whilst studies on the late effect of adrenalectomy avoided this problem, plasma testosterone levels were normal in both adrenalectomised and sham-operated animals. Resetting of anterior pituitary-gonadal relationships may mask the absence of any contribution made by the adrenal gland to testicular steroidogenesis. In contrast to previous data we were unable to demonstrate that adrenalectomy influenced the secretion of testosterone in the male rat.

Adrenalectomy↗

131-I radioiodine therapy for hyperthyroidism in patients with Graves' disease, uninodular goitre and multinodular goitre.

We studied 201 consecutive patients who received a relatively fixed dose of radioiodine for the treatment of hyperthyroidism between the years 1981-6. Patients with Graves' disease (170) were initially treated with a mean (SE) dose of 369 (10) MBq 131-I with a remission rate of 94% at 6 months and a cumulative relapse rate of 12% at one year and 21% at 5 years. The cumulative incidence of hypothyroidism was 26% at 3 months, 55% at 6 months, 61% at 1 year and 66% at 5 years. Patients with a uninodular goitre (10) were initially treated with a mean (SE) dose of 438 (85) MBq 131-I with a remission rate of 100% at 6 months, without relapse at 1 year but relapsing in 17% at 5 years. The cumulative incidence of hypothyroidism was 26% at 3 months, 30% at 6 months, 40% at 1 year and 40% at 5 years. Patients with a multinodular goitre (21) were initially treated with a mean (SE) dose of 613 (77) MBq 131-I with a remission rate of 79% at 6 months and a cumulative relapse rate of 26% at 1 year and 39% at 5 years. The cumulative incidence of hypothyroidism was 5% at 3 months, 14% at 6 months, 24% at 1 year and 24% at 5 years.

Aged↗

The adrenal secretion of progesterone stimulates testicular steroidogenesis in the rat in vitro.

We have used a multicolumn isolated cell superfusion system to investigate the interaction between isolated rat adrenal and testicular cells in the secretion of sex steroids. The steroid responses of a mixed population of adrenal and testicular cells to the administration of ACTH 100 pg/ml was compared with the responses of the separate cell types. Steroid responses from 5 separate experiments were analysed. We have demonstrated increased secretion of 17 alpha-hydroxyprogesterone (P less than 0.0005), androstenedione (P less than 0.05) and testosterone (P less than 0.0005) by a mixture of cells when compared with the responses of either cell type alone. In contrast, the secretion of progesterone (P less than 0.0005) and corticosterone (P less than 0.005) was reduced in the mixed cell population, suggesting that progesterone is preferentially converted by testicular cells to 17 alpha-hydroxyprogesterone, androstenedione and testosterone. This is confirmed by increased secretion of 17 alpha-hydroxyprogesterone, androstenedione and testosterone but not corticosterone by a mixed population following the administration of progesterone 10 ng/ml. These results suggest that the adrenal secretion of progesterone can stimulate testicular steroidogenesis in the male rat in vitro.

Adrenal Glands↗

How effective is external pituitary irradiation for growth hormone-secreting pituitary tumors?

Forty-six patients with GH-secreting pituitary tumours were treated with conventional external pituitary irradiation through two opposed fields to a total dose of 3750 cGy over 15 fractions. Thirty-patients received external radiotherapy as primary treatment and 16 received radiotherapy combined with pituitary surgery. The mean (+/- SD) serum GH in the former group was 74.3 +/- 74.8 mU/l before treatment, falling by 28% per year over 0-5 years and by 16% per year over 0-20 years. The mean (+/- SD) serum GH in the latter group was 265.4 +/- 209.3 mU/l before treatment, falling by 76% in the first year--a direct result of surgical removal of tumour--then by 30% per year over 1-5 years and 16% per year over 1-20 years. Progressive failure of normal anterior pituitary function developed by 10 years, with variable loss of gonadotrophin, corticotrophin and thyrotrophin function. The respective figures for patients treated with radiotherapy alone were 47.4, 29.6 and 16.0% and for the combined group were 70.2, 53.9 and 38.1%. Whilst external pituitary irradiation appears to reduce serum GH concentrations in patients with GH-secreting pituitary tumours the major disadvantages of this form of treatment are the time taken to achieve a cure and the high incidence of hypopituitarism. Nevertheless there did not appear to be any other serious side effects.

Acromegaly↗

The hypothalamic-pituitary-adrenal axis.

Anterior pituitary corticotrophin cells secrete ACTH as part of a larger precursor molecule, pro-opiomelanocortin. Post-translational cleavage of this precursor yields three major peptides: ACTH, beta-LPH and N-POMC. Experiments both in vivo and in vitro suggest that N-POMC may act as a prohormone amplifier for ACTH-induced adrenal steroidogenesis and as regulator of adrenocortical cell growth. The secretion of POMC is under the control of CRF. These findings are discussed in relation to the pathophysiology of corticotrophinoma. The primary defect in this condition appears to reside at the level of the anterior pituitary cell and is readily amenable to treatment by trans-sphenoidal microsurgery. The estimation of plasma ACTH concentrations is proving useful in the monitoring of various clinical conditions including Addison's disease and congenital adrenal hyperplasia.

Adrenal Cortex↗

Atrial fibrillation and isolated suppression of the pituitary-thyroid axis: response to specific antithyroid therapy.

Four patients are described with persistent atrial fibrillation associated with normal plasma total thyroxine (T4) and triiodothyronine (T3) but an absent plasma thyrotrophin (TSH) response to intravenous thyrotrophin releasing hormone (TRH). Initial cardioversion failed to establish sinus rhythm in three of the four patients. Following specific antithyroid therapy to lower thyroid hormone levels sufficient to allow a normal TSH response to TRH sinus rhythm was established in all four patients, one spontaneously and three after cardioversion. Stable sinus rhythm has persisted in three patients over a 2-yr follow-up period. In the presence of atrial fibrillation, an absent plasma TSH response to TRH should be considered sufficient grounds for antithyroid therapy even if plasma total T4 and T3 are within the expected normal range.

Atrial Fibrillation↗

Patterns of plasma cortisol and ACTH concentrations in patients with Addison's disease treated with conventional corticosteroid replacement.

Plasma cortisol and adrenocorticotrophin hormone (ACTH) profiles were estimated in twelve patients with Addison's disease following randomized oral administration of either cortisone acetate (25 mg) or hydrocortisone (20 mg) alternately, at 0900 h on consecutive days. Normal corticosteroid replacement therapy was discontinued from 1200 h on the day prior to the study period. In four patients elevated basal plasma ACTH concentrations were not suppressed to the limit of detection following the administration of either drug, and in three of these no suppression was found following the prolonged administration of pharmacological doses of dexamethasone. Diminished sensitivity of pituitary ACTH secretion to cortisol inhibition may result from chronic loss of negative feedback before and/or after diagnosis and treatment. In three patients elevated basal plasma ACTH concentrations were suppressed adequately during the administration of either drug, but in five, low basal ACTH concentrations following corticosteroid withdrawal suggested chronic inhibition of anterior pituitary corticotrophs by over-replacement with glucocorticoid. However, further study is necessary to determine whether the estimation of ACTH profiles is a more accurate reflection of the adequacy of corticosteroid replacement than the estimation of cortisol profiles alone, and whether this estimation leads to an improvement in patient management. Hydrocortisone (20 mg) achieved higher mean cortisol levels and lower mean ACTH levels than cortisone acetate (25 mg), but either drug may be suitable for glucocorticoid replacement provided the dose is tailored to the individual needs.

Addison Disease↗

The effect of bromocriptine on insulin secretion and glucose tolerance in patients with acromegaly.

The oral administration of bromocriptine 5 mg 6-hourly to twelve patients with acromegaly for a mean period of 12 (range 3-27) months significantly reduced whole blood glucose, plasma insulin and plasma growth hormone (GH) concentrations during a 50 g oral glucose tolerance test (OGTT). After this period of treatment, bromocriptine was withdrawn for 48 h resulting in a significant rise in whole blood glucose, plasma insulin and plasma GH concentrations during a repeat OGTT. It is concluded that bromocriptine therapy improves glucose tolerance in acromegaly by suppressing GH secretion and consequently GH-mediated antagonism of insulin.

Acromegaly↗

The short metyrapone test: comparison of the plasma ACTH response to metyrapone with the cortisol response to insulin-induced hypoglycaemia in patients with pituitary disease.

After a single dose of 2 g metyrapone given with a snack at 2300 h, blood was taken for estimation of plasma adrenocorticotrophin hormone (ACTH) concentrations at 0800 h the next morning from normal individuals and from patients with pituitary disease. Plasma ACTH concentrations following metyrapone were significantly lower in patients with pituitary disease with no evidence of anterior pituitary hormone deficiency (mean 90.0 +/- SD 63.9 ng/l) when compared with normal individuals (mean 182.5 +/- SD 14.1 ng/l, P leads than 0.01) but significantly greater than in patients with pituitary disease in whom a deficiency of one or more anterior pituitary hormones was demonstrated (mean 50.8 +/- SD 14.1 ng/l, P less than 0.01). It is concluded that the short metyrapone test is a sensitive method of detecting minor degrees of impairment of the negative feedback control of aCTH secretion that would be unrecognized by conventional assessment by insulin-induced hypoglycaemia. The clinical relevance of impaired ACTH release in response to a single dose of metyrapone in patients with pituitary tumours, in whom pituitary function is otherwise shown to be adequate, needs to be determined.

Adrenocorticotropic Hormone↗

Combination of potassium iodide and propranolol in preparation of patients with Graves' disease for thyroid surgery.

We assessed the efficacy of the combination of propranolol and potassium iodide in the preparation of patients with Graves' disease for thyroid surgery. Potassium iodide was given orally in a dose of 60 mg three times a day for 10 days before operation in 10 patients who were already receiving propranolol. In contrast to previous experience with either drug used singly, the combined regimen caused a significant fall in mean serum total thyroxine and triiodothyronine to levels in the euthyroid range before operation (P less than 0.001). There was also a significant fall (P less than 0.05) before operation and transient rise after operation in serum reverse triiodothyronine. These preliminary results suggest that the combination of potassium iodide and propranolol may prove to be the optimum preoperative preparation for patients with Graves' disease.

Adult↗

Influence of thyroid status on dopaminergic inhibition of thyrotropin and prolactin secretion: evidence for an additional feedback mechanism in the control of thyroid hormone secretion.

Serum TSH and PRL concentrations were measured after the randomized oral administration of either metoclopramide, L-dopa, or placebo on 3 consecutive days to five patients with overt primary hypothyroidism (low serum total T4 and raised serum TSH) and to five patients with subclinical hypothyroidism (normal serum total T4 and raised serum TSH). In both groups there was a rise in serum TSH and PRL concentrations after metoclopramide and a fall after L-dopa when compared with the effect of the placebo. However, the rise in serum TSH and PRL concentrations was significantly greater in patients with subclinical hypothyroidism compared to that in patients with overt hypothyroidism. It was not possible to show any significant difference in the degree of fall of these pituitary hormones after L-dopa administration in the two groups. These results suggest that in addition to the established negative feedback of thyroid hormones at the level of anterior pituitary thyrotropes, there is a previously unrecognized effect of thyroid hormones at the hypothalamus, resulting in increased dopaminergic inhibition of TSH release. Stimulation of hypothalamic dopamine by thyroid hormones also inhibits PRL secretion.

Feedback↗

The value of islet cell antibody in predicting secondary failure of oral hypoglycaemic agent therapy in Diabetes mellitus.

The sera of 160 diabetics who were well controlled by oral hypoglycaemic agents (OHA) for at least three months after diagnosis were tested for pancreatic islet cell antibodies (ICAb) either at diagnosis or within two years after diagnosis. 129 were non-obese at diagnosis and of these ICAb was detected in the sera in 20 (16%). 31 were obese at diagnosis and of these ICAb was detected in the sera in three (10%). All of the 160 diabetics were insulin independent at the time of testing the serum for ICAb. The presence of ICAb was associated with a high probability of becoming insulin dependent, calculated from actuarial statistics. 86% of ICAb positive patients initially controlled on OHA may be expected to be insulin dependent at five years from diagnosis as compared to 18% of ICAb negative patients. Obesity at diagnosis did not significantly affect the probability of becoming insulin dependent. ICAb positive diabetes controlled by OHA can be regarded as a less severe form of insulin-dependent (Type I) diabetes.

Administration, Oral↗