The changing face of hirsutism.
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Biomedical subjects
Publications and source records attributed to J N Carter.
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To obtain serial blood pressure measurements without trauma in rabbits, we developed a laser-based method which permits noninvasive determination of systolic and diastolic arterial blood pressure. The ease and accuracy of this method were evaluated over a range of blood pressures in five New Zealand White rabbits. Laser-based pressures from the central ear artery were compared with cannula-based pressures from the contralateral central ear artery. Pressures were measured before and during infusions of saline (control), nitroprusside, or epinephrine, and following induction of anesthesia. Noninvasive measurements correlated highly with direct measurements (systole: r = 0.89; diastole: r = 0.93). The difference between the non-invasive and direct pressure measurements during saline, nitroprusside, and epinephrine infusions, and following anesthesia, respectively, were (mean +/- SD, systole/diastole): 4.2 +/- 2.4 (P = NS)/9.3 +/- 1.4 (P less than .001), 4.1 +/- 1.6 (P less than .02)/3.2 +/- 1.1 (P less than .01), 0.6 +/- 2.4 (P = NS)/-3.0 +/- 2.7 (P = NS), and -5.1 +/- 2.9 (P = NS)/0.3 +/- 1.3 (P = NS). The noninvasive method did not result in observable agitation of the animals. To optimize results, visual inspection was required to assure that the instrument's diaphragm was not deformed or dried from previous use, and that the diaphragm was placed over the center of the arterial lumen. It was also necessary to dim room lights and to direct heating lights away from the ears to avoid degrading light signal quality. These results, albeit involving a small number of animals, indicate the potential utility of this method in the study of chronic pathophysiological processes requiring long-term repeated determination of systolic and diastolic blood pressure.
To study the time course of left ventricular structural and functional responses to chronic aortic regurgitation, aortic regurgitation was surgically induced in rabbits, and Doppler echocardiography was performed preoperatively and serially postoperatively for up to 2.5 yr. Twenty-five New Zealand White rabbits underwent surgical induction of aortic regurgitation and 13 control animals underwent sham operation. Left ventricular endocardial and epicardial surfaces were digitized from M-mode echocardiograms to measure the rates of change of cavity dimensions and wall thicknesses during diastolic relaxation and systolic contraction. Aortic regurgitant animals developed left ventricular dilatation and eccentric hypertrophy that remained relatively stable throughout the follow-up period. Compared with baseline values, left ventricular mass increased 120% and left ventricular internal dimension at end diastole increased 40%, whereas posterior wall thickness at end diastole and fractional shortening remained relatively stable. Left ventricular diastolic performance was enhanced at 6 mo after operation, a finding associated with increased volume load and heart rate following induction of aortic regurgitation. Diastolic performance was then reduced at 12 mo after operation and demonstrated no further decline throughout the remainder of the follow-up period. In contrast, left ventricular systolic performance was not altered following operation and remained preserved until the final assessment at up to 2.5 yr. Thus alterations in diastolic performance occurred without impairment of systolic performance during long-term follow-up of chronic experimental aortic regurgitation.
Serum concentrations of dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHA-sulfate), cortisol, prolactin, and growth hormone were measured at half-hour intervals for 24 hr in five healthy children aged 8--13 yr. Their adolescent development was assessed by clinical staging, plus determinations of serum FSH, LH, testosterone and estradiol during both wakefulness and sleep. Correlative analysis indicates that there was synchronous secretion of DHA and cortisol, implying regulation of both by ACTH. With advancing age and sexual maturation, there was a progressive rise in mean serum DHA and DHA-sulfate levels, but no similar change in serum cortisol concentrations. There was evidence for enhanced secretion of both growth hormone and prolactin during sleep in all subjects (including one who was hyperprolactinemic), but there was no obvious relationship between levels of these pituitary hormones and the early pubertal rise in adrenal androgens.
We studied 22 men with prolactin-secreting pituitary tumors and hypogonadism. Twenty complained of impotence, nine had visual impairment, and three experienced galactorrhea. None of the 17 patients undergoing operation or radiotherapy, or both, were subsequently normoprolactinemic. In all 13 patients treated with bromocryptine major clinical improvement was associated with a decrease in serum prolactin levels and in nine with an increase in serum testosterone. Two patients receiving testosterone replacement therapy showed improved potency only after bromocryptine was administered. The results indicate that hyperprolactinemia frequently induces hypogonadism in men, that bromocryptine ameliorates symptoms of disease previously unchanged by operation or radiotherapy, and that the impotence observed may not be solely the result of hypogonadism.
Alterations in plasma prolactin (PRL) concentrations in response to nursing in puerperally lactating women are often significant beyond the 90th postpartum day, yet the increment appears unrelated to the frequency or duration of the nursing stimulus. Tonic gonadotropin secretion is low, assuming a more episodic secretory pattern either when the frequency of breast-feeding is reduced or when weaning takes place. Significant increments in peripheral concentrations of luteinizing hormone can be seen in response to weaning coincident with a fall in peripheral plasma PRL concentration. At the same time, peripheral estrogen concentrations increase, suggesting that a specific set point for ovarian responsiveness to gonadotropins exists. Whether this set point is related solely to the peripheral concentration of gonadotropins or whether it is also related to the peripheral PRL concentration is not known at this time.
Serum concentrations of dehydroepiandrosterone, DHA sulfate, estradiol, and prolactin in 20 girls with precocious adrenarche were compared with those of healthy girls of varying age and degrees of breast and sex hair development. Production of adrenal androgens, as reflected by serum DHA and DHA-sulfate concentrations, was significantly increased in PA above that in age-matched control subjects. Surprisingly, in spite of their lack of breast growth, the patients with PA also had serum estradiol levels that were higher than in the prepubertal girls and similar to those found in girls with both breast and pubic hair development. Serum prolactin concentrations in the patients with PA were not increased over those of the age-matched (less than 8 years) prepubertal girls. In the older prepubertal ( greater than 8 years) and early pubertal girls serum prolactin levels were lower. The finding of increased estradiol levels suggests that precocious adrenarche is not a distinct endocrine entity, but merely represents a variant of early adolescence in which estrogen secretion is sufficient to influence adrenal 3beta-hydroxysteroid dehydrogenase activity with a resultant rise in DHA production, but not sufficient to produce clinically apparent breast changes. The data do not support a similar role for prolactin.
Ovine prolactin (oPRL) increased serum somatomedin (SM) bioactivity in hypophysectomized female rats. ACTH, in small but not large doses, augmented this oPRL effect. These results suggest that in the female rat PRL may regulate SM production. Adrenal factors may variably modulate SM production or serum SM bioactivity.
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Clinically euthyroid patients with severe, chronic, non-thyroidal illnesses usually have decreased serum total and absolute free T3 concentrations. Since T3 is the metabolically more active of the two thyroid hormones, it has been suggested that these patients may be hypothyroid and thus may benefit from T3 therapy. To test this hypothesis, five patients with chronic renal failure requiring maintenance haemodialysis were treated with 5 microgram T3 eight hourly, increasing at three weekly intervals to 10 microgram eight hourly, 20 microgram eight hourly and finally 30 microgram eight hourly. The mean +/- SD serum T3 level did not change over the 12 week period (1.42 +/- 0.17 vs. 1.41 +/- 0.26 nmoll-1 whilst the mean serum T4 and TSH levels fell from 87.0 +/- 15.2 to 47.5 +/- 18.8 nmoll-1 and 1.9 +/- 0.9 to 1.3 +/- 1.6 mUl-1 respectively. Only the change in T4 levels was significant (P less than 0.005). A significant decrease in mean serum T4 levels was apparent even after the treatment period with 5 microgram T3 eight hourly (87.0 +/- 15.2 vs. 51.2 +/- 15.7; P less than 0.005). The mean fasting serum triglyceride level fell from 1.16 +/- 0.74 to 0.94 +/- 0.74 mmoll-1 (P less than 0.05) and the mean fasting serum cholesterol level fell from 6.06 +/- 1.13 to 4.69 +/- 1.10 mmoll-1 (P less than 0.05). There were no subjective improvements in any of the patients. From the marked changes in serum T4 levels during the administration of T3, it is concluded that, prior to treatment, the patients were biochemically euthyroid and not hypothyroid and thus did not require T3 therapy.
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To study the effects of prolactin (PRL) on adrenocortical function in humans, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), androstenedione (delta) and testosterone (T) were measured in serum obtained from 35 hyperprolactinemic women with galactorrhea and amenorrhea before and after treatment with bromocriptine-induced fall in mean PRL levels from 82 +/- 8 (SE) to 14 +/- 2 ng/ml (n = 39, P less than 0.0005), DHAS fell from 322 +/- 21 to 237 +/- 21 microgram/dl (n = 39); P less than 0.0005), DHA fell from 492 +/- 47 to 378 +/- 30 ng/dl (n = 39; P less than 0.01) while T (n = 16) and delta (n = 13) levels were unchanges (44 +/- 4 vs. 49 +/- 4 ng/dl and 280 +/- 55 vs. 236 +/- 40 ng/dl, respectively). In addition, 4 women were infused iv with 25 microgram synthetic ACTH over 4 h and serial blood samples drawn while hyperprolactinemic, and again 2-4 months later following normalization of PRL levels by bromocriptine. Although pre-infusion levels of DHAS were lower when PRL levels were normalized, no significant differences in responses of circulating DHAS, DHA, T, cortisol and 17-hydroxyprogesterone concentrations were detected between the two infusions. Since DHAS is virtually an exclusive product of the adrenal cortex, and since high PRL levels appear to inhibit ovarian steroid production, the findings suggest that hyperprolactinemia selectively stimulates adrenocortical androgen production.
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Many clinically euthyroid patients with severe, chronic, non-throidal illnesses (i.e. sick euthyroid patients) have very low circulating concentrations of total and absolute free triiodothyronine (T3), low-normal concentrations of total thyroxine (T4), elevated concentrations of absolute free T4, and circulating concentrations of thyrotrophin (TSH) that are either normal or subnormal. This study was undertaken to elucidate the mechanism of the low circulating T3 concentrations. The disappearance rate of 125 I-T3 from the circulation of five representative sick euthyroid patients was studied and found to be slower, but not significantly so, compared with three control subjects, thus excluding an increased destruction rate as the cause of the low T3 levels. A selective decrease of T3 secretion from the thyroid gland of these patients was also excluded by the results of TSH stimulation tests. Inhibition of extra-thyroidal conversion of T4 to T3 was suggested by studies of the thyroid function in a hypothyroid woman with a Grade IV lymphoma on T4 replacement therapy. When the lymphoma was in remission, her circulating T3 concentration was 2-55 nmol/l but when it relapsed it fell to 0-55 nmol/l. The T4 concentrations were 124-7 nmol/l and 126 nmol/1 respectively. Decreased monodeiodination of T4 to T3 in sick euthyroid patients was confirmed by paper chromatography of extracted serum obtained 48 h after an i.v. injection of 125 I-T4 into two severely ill patients from the intensive therapy unit and a control subject. Peaks of radioactivity corresponding to 125 I-T4 and 125 I-T3 were detected in the control subject, but only a single peak corresponding to 125 I-T4 was detected in the ill patients.
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An approach to the management of patients with thyroid storm is described. The treatment regimen, which is directed against the abnormalities as they are presently understood, incorporates: (a) Propranolol to inhibit the catecholamine-mediated peripheral effects of the circulating thyronines; (b) Propylthiouracil to inhibit thyroid hormone synthesis and to inhibit peripheral conversion of thyroxine to triiodothyronine (T3), the predominant source of T3 production; (c) Iodine to block the glandular release of thyroid hormones; (d) Dexamethasone along with general supportive therapy. The regimen has been used for a 13 year old schoolgirl with thyroid storm, and the induced rapid fall in serum T3 levels is illustrated. It has also been used in patients with florid thyrotoxicosis undergoing emergency surgery and has resulted in marked clinical improvement associated with rapid decreases in serum T3 levels. It is a simple and efficient regimen, rendering cumbersome forms of therapy such as plasmapheresis and peritoneal dialysis unnecessary.