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Biomedical subjects

J Wortsman

Publications and source records attributed to J Wortsman.

At least 91 records · Page 5Linked to original sources

Effects of elevated gonadotropin levels on thyroid function in the male rat.

In order to determine if thyroid disease in hypogonadal men is the result of chronic elevation of serum gonadotropins, thyroid histology and serum thyroid hormone levels were evaluated in male rats that had been castrated either 2 weeks or 15 months previously. Despite significantly elevating serum LH levels, castration did not affect thyroid structure or function. Serum total T4 levels were reduced with age in both short and long-term castrate animals but returned to the levels seen in young rats when testosterone was replaced. Testosterone replacement also increased free T4 levels in both the young and old castrate rats. Neither age nor testosterone replacement affected serum T3 or TSH levels.

Animals↗

Epidermal autoantibodies in erythema multiforme.

We report a case of refractory erythema multiforme associated with atypical epidermal autoantibodies. The patient was a 63-year-old woman with clinical and histologic features of erythema multiforme and a large mediastinal T cell lymphoma. Immunofluorescence studies disclosed high serum titers of cell surface antibodies against epidermal keratinocytes in a pattern typical of pemphigus vulgaris. The epidermal antigen reacting with these circulating antibodies was characterized by incubating 14C-labeled keratinocytes with serum. The patient's serum pattern precipitated multiple proteins keratinocytes antigens), but not the 130,000- and 85,000-dalton polypeptides characteristic of pemphigus vulgaris. Thus autoantibodies reacting selectively with non-pemphigus vulgaris epidermal keratinocyte antigens may be the cause of a false-positive immunofluorescence test for pemphigus vulgaris.

Aged↗

Hypogonadism following long-term treatment with diethylstilbestrol.

The authors describe the abnormalities of gonadal function developing in a patient with prostate cancer who had received estrogen therapy continuously for 6 years. The pretreatment prostate biopsy showed well developed acini consistent with normal androgenization and adenocarcinoma. Twelve years later, 6 years after discontinuation of estrogen treatment, the patient presented with severe hypogonadism, gynecomastia, and primary hypothyroidism. Testicular biopsies showed ghosts of seminiferous tubules with absence of Leydig cells, and prostatic biopsies showed atrophic acini without evidence of malignancy. Despite undetectable serum testosterone levels, serum gonadotropins were inappropriately normal and responded minimally to gonadotropin-releasing hormone (GnRH) administration. Replacement therapy with levothyroxine did not correct gonadal dysfunction. Thus, prolonged estrogen therapy may result in irreversible testicular destruction and loss of the feed-back response of the hypothalamic pituitary gonadal axis.

Adenocarcinoma↗

Persistence of large molecular weight prolactin secretion during pregnancy in women with macroprolactinemia and its presence in fetal cord blood.

Two hyperprolactinemic women with marked increases in circulating 150K PRL were studied from conception throughout pregnancy and delivery. The serum PRL increase during pregnancy in these women was considerably less than that in normal pregnant women (2- and 3.5-fold vs. 10- to 20-fold increases, respectively). The 150K PRL species persisted as the predominant circulating form of PRL throughout each trimester of pregnancy in these women. In contrast, the predominant form of PRL in serum from normal pregnant women was the 22K PRL form. Gel filtration analysis of the umbilical venous cord serum of infants of the macroprolactinemic women demonstrated excessive concentrations of 150K and 50K PRL compared to the molecular species of PRL in the cord serum of normal infants. Repeat analysis of the PRL species in one infant at age 3 yr continued to reveal excessive secretion of 150K PRL (11% vs. less than 6% in normals). These data suggest that genetic influences may be operative in determining PRL heterogeneity.

Adult↗

In vivo threshold for cutaneous synthesis of vitamin D3.

Cutaneous vitamin D3 synthesis and release into the circulation is promoted by skin exposure to ultraviolet B radiation (UVB, spectrum 290 to 320 nm). To determine the relation between UVB energy level and cutaneous vitamin D synthetic response, we delivered graded increases of UVB suberythemic radiant energy (3 to 27 millijoules/cm2 [mJ/cm2]) to 32 untanned young white subjects with skin type III (Fitzpatrick-Pathak classification). Serum vitamin D3 was determined 1 hour before (basal value) and 24 hours after a single whole body exposure to UVB in a phototherapy unit. The basal vitamin D3 concentration was similar in all individuals (mean +/- SEM for whole group, 1.6 +/- 0.2 ng/ml). UVB irradiances were followed by proportional rises in serum vitamin D3 (at 27 mJ/cm2, 14.3 +/- 3.7 ng/ml), and the overall correlation between UVB radiation and consequent serum vitamin D3 response (r = 0.81; p less than 0.02) was best described by an exponential function. The minimal UVB radiation level that produced a significant increase in serum vitamin D3 was 18 mJ/cm2, a value similar to the lowest solar broadband UVB irradiance that generates previtamin D3 in vitro from the precursor 7-dehydrocholesterol (20 mJ/cm2). Because in the northern United States winter UVB irradiance does not generally reach this threshold level, we conclude that individuals living at extreme northern (or southern) latitudes may have higher dependence on body stores and dietary supply to meet their vitamin D requirements during winter.

Adult↗

Coexistence of polycystic ovary syndrome and pelvic endometriosis.

Pelvic endometriosis was observed in 15 of 91 women (16.5%) with laparoscopically confirmed polycystic ovary syndrome. There were no significant clinical differences among those with and those without endometriosis. The groups were of similar age, parity, and ponderal indices and had similar incidences of oligomenorrhea, hirsutism, and infertility; the serum concentrations of LH, FSH, LH/FSH, prolactin, testosterone, and dehydroepiandrosterone sulfate were also similar in each group. However, women with polycystic ovaries and endometriosis presented more frequently with regular menses (40 versus 14.5%; P = .05) and less frequently with secondary amenorrhea (0 versus 38.2%; P = .05) and galactorrhea (0 versus 9.2%; P = .05) than the women with polycystic ovaries alone. Endometriosis appears to be a coincidental finding in polycystic ovary syndrome, and its development does not modify significantly the clinical picture or biochemical profiles of these patients. However, menstrual patterns seem to be affected.

Adult↗

Thermal inactivation of L-thyroxin.

We assessed the extent of inactivation of L-thyroxin induced by exposure to heat in the presence of two vehicles. Preparations of L-thyroxin in the dry powder form, or dispersed in the solvents propylene glycol (water-like) or ethoxylated castor oil (oil-like), were heated at temperatures ranging from 65 to 160 degrees C, for 5- to 15-min periods. Heating L-thyroxin to a temperature below that of cooked bovine ground meat (72 degrees C) produced less than 10% degradation. Thermal degradation was pronounced only above 90 degrees C, and was almost completed at 160 degrees C. L-Triiodothyronine was the only thermal degradation product identified after L-thyroxin was heated at 125 degrees C. In a separate experiment we measured the melting point of L-thyroxin, 148.81 degrees C. This value agrees closely with the observed thermal sensitivity. We conclude that L-thyroxin is not significantly degraded under conditions encountered during cooking of ground bovine meat for short times at moderate temperatures.

Animals↗

Long-term assessment of patients with macroprolactinemia.

Three patients presenting with hyperprolactinemia associated with normal menses, retained fertility, and minimal lactation were followed for a period of 5 to 7 years. All had associated thyroid autoimmune disorders (one with chronic thyroiditis and two with Graves' disease). Their major form of circulating prolactin (PRL) was in the large-molecular weight (150K) form (macroprolactinemia). Whereas normal serum content of 150K PRL is less than 10% of the total, these three patients had 150K PRL fractions of 97%, 96%, and 67%. The retention of normal menses and fertility of these subjects suggested that the 150K PRL had diminished biologic activity as patients with elevations of 22K PRL will have amenorrhea and infertility. Over time, the serum PRL levels of these three patients decreased with a coincident fall in the percentage of 150K PRL. Although serum thyroid concentrations usually influence serum PRL levels, no such effects were seen in these patients whether they were hypothyroid or hyperthyroid, neither was a causal relationship between the macroprolactinemia and autoimmune thyroid disease established. Macroprolactinemia cannot be considered to be a completely benign condition as occasionally it may be associated with infertility and osteopenia.

Adult↗

Ultrastructural characteristics of keloid fibroblasts.

Myofibroblasts abound in granulation tissue, where they play an important role in the healing process. We evaluated the characteristics of fibroblasts in ten patients with keloids, a disorder of skin wound repair. Keloid lesions uniformly exhibited numerous fibroblasts with prominent Golgi complexes and abundant rough endoplasmic reticulum. Although rare fibroblasts exhibited a convoluted nucleus and tangled microfilaments, none could be characterized as myofibroblast, as defined by cytoplasmic myofilaments and cell to cell junctions. We conclude that fibroblast density and activity are increased in keloids, but true myofibroblasts are not a component of these lesions.

Adult↗

Lack of effect of exogenous calcitriol on the cutaneous production of vitamin D3.

Synthesis of vitamin D3 is determined primarily by cutaneous exposure to UV light irradiation (UVR). We studied the effect of exogenous 1,25-dihydroxyvitamin D on the cutaneous synthesis of vitamin D. Eight normal subjects, all caucasian, were randomly assigned to receive 1,25-dihydroxyvitamin D (0.5 micrograms daily) or no treatment for 20 days, followed 30 days later by the other treatment for 20 days. After 5 days, each experimental group (untreated and calcitriol treated) was exposed to one minimal erythema dose of UVR (UVR amplification test). Serum vitamin D3 concentrations reached peak levels 24 h after UVR exposure, and the mean values in the untreated and calcitriol-treated subjects were similar: 13.5 +/- 0.6 (+/- SD) ng/mL (35.1 +/- 1.5 nmol/L) and 13.0 +/- 0.6 ng/mL (33.8 +/- 1.5 nmol/L), respectively (P greater than 0.1). An identical 24-h post-UVR serum vitamin D3 value [13.5 ng/mL (35.0 nmol/L)] was found in a hypoparathyroid patient taking calcitriol (1 microgram daily). Thus, the cutaneous synthesis of vitamin D3 in response to acute UVR exposure was not inhibited by the administration of 1,25-dihydroxyvitamin D orally.

Adult↗

Effect of adrenal function on gastrointestinal peptide release in experimental cardiac arrest.

Pancreatic polypeptide (PP), neurotensin, substance P, and vasoactive intestinal polypeptide (VIP) are peptides that modify various autonomic and neural functions. These substances are secreted into the blood in response to physiologic stimuli affecting the gastrointestinal tract. To determine the effect of adrenal hormones on gastrointestinal peptide release we measured blood levels of PP, VIP, substance P, and neurotensin in adrenalectomized and intact dogs undergoing cardiac arrest and cardiopulmonary resuscitation (CPR), a condition associated with maximal adrenal stimulation. One hour after completion of abdominal surgery consisting of bilateral adrenalectomy or exposure of the adrenal glands (sham operation), ventricular fibrillation was induced in 19 dogs by direct ventricular discharge. Despite marked elevations of plasma epinephrine and norepinephrine, CPR was associated with minimal endocrine gastrointestinal involvement, restricted to increased VIP levels in sham-operated dogs. No specific gastrointestinal peptide response to cardiac arrest was seen in adrenalectomized animals, but their plasma PP and VIP levels were higher than those of sham-operated dogs. Therefore, acute maximal adrenal stimulation is associated with selective VIP release. In addition, the higher level of the vagally controlled plasma PP in adrenalectomized animals suggests a tonic inhibitory effect of adrenal secretions on the release of this peptide.

Adrenal Glands↗

Chronic sunscreen use decreases circulating concentrations of 25-hydroxyvitamin D. A preliminary study.

Sunscreens block the absorption of the sunlight spectrum responsible for the cutaneous synthesis of vitamin D (ultraviolet B). The present study was prompted by our observation of suppression of cutaneous vitamin D formation by a single application of sunscreening agents. We measured the index of vitamin D body store, serum 25-hydroxyvitamin D (25-OH-D) level, in 20 long-term users of p-aminobenzoic acid (PABA) and in 20 controls matched by age and exposure to sunlight. Serum 25-OH-D levels were significantly lower among long-term PABA users than among normal controls: 40.2 +/- 3.2 vs 91.3 +/- 6.2 nmol/L. Furthermore, vitamin D deficiency, ie, 25-OH-D levels below 20.0 nmol/L, was seen in two PABA users and in none of the controls. This preliminary study suggests that long-term use of PABA may be associated with low body stores of vitamin D in some persons.

Adult↗

Apparent isolated elevation of serum triiodothyronine level in a patient with a thyroid nodule.

Cystic thyroid nodules most commonly occur with a euthyroid state and appear as cold lesions on radioactive iodine scan. I describe a 32-year-old woman who presented during the third trimester of her second pregnancy with a toxic cystic lesion of the thyroid. In studies performed post partum, the serum free thyroxine (T4) index was normal, while the triiodothyronine (T3) level was elevated and thyrotropin level was low and unresponsive to thyrotropin-releasing hormone stimulation. Iodine 123 thyroid scan demonstrated localized nonsuppressible uptake over the nodule. Multiple echo-free (fluid-filled) cavities were observed by ultrasound study. Thyroid lobectomy demonstrated a thyroid colloid nodule with areas of cystic degeneration containing hyperplastic papillary projections. Postoperatively, the patient developed transient hypothyroidism followed by spontaneous recovery to euthyroidism with normal function of the suppressed gland. Blood obtained from the venous effluent of the thyroid nodule had extremely high T3 and T4 concentrations: 359.1 nmol/L and 2420 nmol/L, respectively, while peripheral venous blood showed isolated elevation of T3, to 4.6 nmol/L (normal, 1.2 to 3.1 nmol/L), and a normal T4 level of 116 nmol/L (normal, 64 to 154 nmol/L). Serum T3 and T4 thyroidal/peripheral ratios were close to one in two euthyroid patients undergoing neck surgery. Thus, thyroid nodules may present with isolated elevation of serum T3 levels despite increased thyroidal release of T4.

Adult↗

Abnormal testicular function in men with primary hypothyroidism.

Myxedema in men is thought to cause infertility and impotence. Testicular function was investigated in eight consecutive men with primary hypothyroidism (autoimmune thyroiditis in five patients and amiodarone therapy in three patients). All had impotence that preceded the onset of hypothyroidism and did not improve with thyroid therapy. Gonadal function tests showed a hypergonadotropic state in five patients and hypogonadotropic hypogonadism in three patients including one with no response to luteinizing hormone-releasing hormone. Luteinizing hormone bioactivity was decreased in six patients and increased in two subjects who also had increased luteinizing hormone immunoreactivity. Serum testosterone and testosterone/estradiol-binding globulin concentrations were low in four of the patients. It is concluded that abnormalities of gonadal function are common in men with primary hypothyroidism.

Adult↗

Antibodies against the insulin receptor in paraneoplastic acanthosis nigricans.

Acanthosis nigricans is a skin disorder associated with endocrine abnormalities, autoimmune disease, and systemic malignancies. Insulin resistance is a common accompaniment of the nonmalignant varieties of acanthosis nigricans. A 44-year-old man is described with a functioning metastatic pheochromocytoma, acanthosis nigricans, and insulin-resistant diabetes mellitus. Studies of insulin action showed a low titer of anti-insulin antibodies and a very high titer of antibodies against the insulin receptor. This case documents for the first time insulin resistance due to anti-insulin receptor antibodies in a paraneoplastic variety of acanthosis nigricans.

Acanthosis Nigricans↗