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Biomedical subjects

J Wortsman

Publications and source records attributed to J Wortsman.

At least 109 records · Page 6Linked to original sources
PubMed1987

Spectrum of endocrine abnormalities associated with acanthosis nigricans.

Acanthosis nigricans is a marker for disorders of insulin action, endocrine abnormalities, and cancer of internal organs. To evaluate the clinical significance of this marker the systemic alterations and clinical features of 26 patients with acanthosis nigricans seen at two institutions were reviewed. Most subjects affected by acanthosis nigricans were female (20 patients), Caucasian (22 patients), in the third decade of life (13 patients), and overweight (24 patients greater than 120 percent ideal body weight). Gonadal disease, present in 17 patients, was expressed as polycystic ovary syndrome (11 cases), disorders of prolactin secretion (two cases, one with polycystic ovary syndrome), streak gonads (one case), and hypogonadism of the male (four cases). Thyroid disease and tinea versicolor were present in four patients each. Three patients were receiving insulin therapy for diabetes mellitus, and in two additional patients diabetes mellitus was detected during the diagnostic workup. All patients had elevated fasting insulin levels; most of them also had an exaggerated insulin response to a glucose load. Two of 18 patients tested had antibodies against the insulin receptor in the circulation. Skin biopsy of acanthosis nigricans lesions from all 26 patients showed a typical pattern of hyperkeratosis, acanthosis, and epidermal papillomatosis. Colloidal iron staining showed glycosaminoglycan infiltration of the papillary dermis (21 of 21 cases), consisting mainly of hyaluronic acid. It is concluded that: (1) hyperinsulinenemia and local dermal glycosaminoglycan deposition are regular features in acanthosis nigricans and (2) patients with acanthosis nigricans should be screened for diabetes mellitus, gonadal disease, and hypothyroidism.

Acanthosis Nigricans↗
PubMed1987

Cerebrospinal fluid changes in experimental cardiac arrest (maximal stress).

Cardiac arrest produces a prompt and maximal increase of plasma catecholamines, with associated elevations of the hormones involved in the endocrine response to stress. To investigate the participation of the central nervous system (CNS) in the generation of the endocrine response, the catecholamines epinephrine and norepinephrine in cerebrospinal fluid (CSF) were measured before, during, and after cardiac arrest accompanied by cardiopulmonary resuscitation (CPR) in adrenalectomized (ADX) and sham-operated (SHAM) dogs. We also determined the activity of acetylcholine esterase (AChE), an intracellular enzyme released into the CSF after hypothalamic or caudate stimulation. During CPR, plasma epinephrine increased significantly in SHAM but not ADX dogs, increasing from (mean +/- SE) 480 +/- 171 to 29,800 +/- 14,200 pg/ml (P less than 0.05). Prearrest CSF norepinephrine was higher in ADX than SHAM dogs and increased in both groups with cardiac arrest, but the increase was significant only in SHAM animals; CSF epinephrine remained unchanged during or after cardiac arrest. CSF AChE activity increased during and after defibrillation; the difference with basal levels became significant when the peak postarrest values were considered (P less than 0.05). These results document biochemical changes occurring in the CNS during maximal stress represented by cardiac arrest. It is suggested that CSF norepinephrine and AChE activity elevations are markers for hypothalamic activation from the stress of cardiac arrest.

Acetylcholinesterase↗
PubMed1987

Plasma catecholamine and serum cortisol responses to experimental cardiac arrest in dogs.

The plasma catecholamine and serum cortisol responses to cardiac arrest (ventricular fibrillation), cardiopulmonary resuscitation (CPR), and ventricular defibrillation were examined in 10 intact (sham-operated controls) and 10 bilaterally adrenalectomized dogs. One hour after surgery, the cardiac ventricles were electrically fibrillated, and 30 s later Standard American Heart Association CPR was begun. After 12 min of CPR, the ventricles were defibrillated. Cardiac arrest per se results in a massive increase in plasma epinephrine and norepinephrine concentrations and indicates that the adrenal medullas are the predominant source of this response. Although the epinephrine response was virtually nonexistent in the adrenalectomized dogs, the norepinephrine response was approximately 30% of that in the sham-operated control animals. Thus there is an adrenomedullary, and perhaps a sympathetic neural, component to the sympathochromaffin response to cardiac arrest. Resuscitation from experimental cardiac arrest tended (P greater than 0.05 less than 0.1) to be lower in the adrenalectomized dogs (1 of 10) than in the animals with intact adrenal glands (6 of 10).

Animals↗
PubMed1987

Sunscreens suppress cutaneous vitamin D3 synthesis.

Sunscreens block the cutaneous absorption of UV-B radiation and prevent sunburning, premature aging, and cancer of the skin. Inasmuch as UV-B radiation is also responsible for the photosynthesis of vitamin D3, we investigated the effect of sunscreens on the cutaneous formation of vitamin D3 in vivo and in vitro. Eight normal subjects, four of whom had been protected with the sunscreen para-aminobenzoic acid (sun protection factor 8), were exposed to one minimal erythema dose of UV radiation. The mean serum vitamin D3 concentration increased from 1.5 +/- 1.0 (+/- SEM) to 25.6 +/- 6.7 ng/mL in unprotected subjects, whereas it was 5.6 +/- 3.0 and 4.4 +/- 2.4 ng/mL at these times in the subjects who were protected with para-aminobenzoic acid. Para-aminobenzoic acid also prevented the photoisomerization of 7-dehydrocholesterol to previtamin D3 in human skin slices in vitro. These results indicate that the sunscreen interferred with the cutaneous production of vitamin D3.

4-Aminobenzoic Acid↗
PubMed1987

Hypothyroxinemia in cardiac arrest.

Thyroid function was evaluated in cardiac arrest (CA), a condition associated with marked activation of the pituitary-adrenal axis. Blood samples were obtained in 24 patients immediately after diagnosis of CA and again ten minutes later. Samples were also obtained from 22 patients admitted consecutively to the intensive care unit (ICU). Abnormalities of thyroid indexes among patients on the ICU who had not experienced CA were low triiodothyronine (T3) in 45%, low thyroxine (T4) in 32%, low free T4 (equilibrium dialysis) in 21%, and elevated reverse T3 levels in 36%. The alterations of thyroid values were both more common and marked in patients with CA, with abnormally low T3 in 84% of the patients, low T4 in 65%, low free T4 in 65%, and high reverse T3 in 80%. Thyroxine-binding globulin and prealbumin concentrations were below the normal range in 40% and 21% of patients with CA. A thyroid hormone-binding inhibitor was detected in 38% of patients with CA. Thyroglobulin level was slightly high in patients with CA but not significantly different from controls on the ICU. The abnormalities present at zero minutes were further exaggerated ten minutes after CA. We conclude that abnormalities on tests measuring thyroid function are extremely common during the cardiovascular emergency of CA.

Adult↗
PubMed1986

Parathyroid cell surface autoantibodies that inhibit parathyroid hormone secretion from dispersed human parathyroid cells.

Serum autoantibodies directed toward antigenic determinants on the surface of human parathyroid cells (PTAb-CS) have been demonstrated in a subset (8 of 23) of adult patients with idiopathic hypoparathyroidism (IHP). In sera from 3 of 8 patients with PTAb-CS, binding of these autoantibodies to their respective parathyroid cell surface antigen(s) resulted in marked inhibition of parathyroid hormone (PTH) secretion in an in vitro dispersed human parathyroid cell (dPTC) system. In 1 subject evaluated longitudinally, circulating levels of PTAb-CS, and the magnitude of the inhibitory effect on PTH secretion, temporally correlated with the clinical course of the hypoparathyroidism. These findings suggest a causative role for antibodies directed against cell surface antigens in parathyroid dysfunction in some cases of "autoimmune" hypoparathyroidism.

Aged↗
PubMed1986

Acanthosis nigricans, hypothyroidism, and insulin resistance.

Acanthosis nigricans has been associated with multiple endocrinopathies. The common denominator appears to be insulin resistance. Three patients are described (one woman and two men) who presented with hypothyroidism and acanthosis nigricans. All the patients had elevated insulin levels in the fasting state and in response to an oral glucose load. The mechanism for the resistance to insulin was a post-receptor binding defect or a structural abnormality in circulating insulin, since glucose tolerance and plasma cortisol, somatomedin, growth hormone, and insulin receptor concentrations in peripheral monocytes were all normal. Antibodies to insulin or the insulin receptor were absent. Neither insulin resistance nor acanthosis nigricans diminished following correction of the hypothyroidism. It is concluded that hypothyroidism may be associated with acanthosis nigricans, that hyperinsulinemia is a regular correlate of the skin disorder, and that treatment of the hypothyroidism does not resolve the hyperinsulinemia or the acanthosis nigricans.

Acanthosis Nigricans↗
PubMed1986

Increased incidence of thyroid disease among men with hypergonadotropic hypogonadism.

An association between hypothyroidism and hypogonadism has been described in the syndrome of autoimmune polyglandular failure and in Klinefelter's syndrome. The incidence of thyroid disease among males with hypogonadism was evaluated. Patients were divided into those with hypergonadotropic hypogonadism (Group I; n = 19) and those with isolated hypogonadotropic hypogonadism (Group II; n = 17), according to their serum concentrations of follicle-stimulating hormone, luteinizing hormone, and testosterone. Nine cases of thyroid diseases were encountered in Group I; these included benign and malignant thyroid tumors, hypothyroidism due to Hashimoto's thyroiditis, and hypothyroidism due to amiodarone therapy. Only one case of thyroid disease (hypothyroidism due to Hashimoto's thyroiditis) was found in Group II (p less than 0.01). Patients of Group I were also significantly older than patients of Group II (51 +/- 4 versus 37 +/- 4 years; p less than 0.01); and patients with thyroid diseases were also older than those without thyroid disorders (60 +/- 6 versus 43 +/- 6 years, p less than 0.1). It is concluded that older subjects with hypogonadism and long-term elevation of levels of serum gonadotropins should undergo careful evaluation of thyroid gland morphology and function.

Adult↗
PubMed1986

Modulation of thyroid parameters by exogenous thyroxine in familial dysalbuminemic hyperthyroxinemia.

A patient with familial dysalbuminemic hyperthyroxinemia (FDH) was given graded doses of exogenous thyroxine (0.2 mg/d for 2 weeks; 0.4 mg/d for 2 weeks; 0.6 mg/d for 2 weeks) to study modulation of various thyroid parameters. The plasma concentration of the serum transport proteins, thyroxine binding globulin (TBG), sex hormone binding globulin (SHBG), and cortisol binding globulin (CBG) as well as serum thyroxine (T4), triiodothyronine (T3), absolute free thyroxine (FT4), and serum protein binding of T4 tracer were measured. At the end of T4 treatment, T4 and T3 were increased by 151% and 78%, respectively. The FT4 increased (157%), while the percent dialyzable free T4 fraction (DFT4) showed no significant change. SHBG, a protein sensitive to thyroid hormone (TH) action, increased 148% (from 0.23 to 0.57 micrograms/dL) after treatment but this concentration was still in the normal range; TBG and CBG decreased by about 16%. Analysis of the electrophoretic 125I-T4 distribution pattern in serum during T4 treatment showed essentially no change in TBG-bound T4 (percent tracer carriage X total T4), while there was a progressive increase in albumin-bound T4 (341% increase over pretreatment value) and a lesser increase in prealbumin (TBPA)-bound T4 (187%). These observations describing alterations in TH action, serum T4-protein binding, and the failure of percent DFT4 to increase with elevation in serum total T4 are of clinical significance in evaluating thyroid function parameters in FDH patients undergoing TH treatment.

Adult↗
PubMed1986

Suppression of testosterone-estradiol binding globulin by medroxyprogesterone acetate in polycystic ovary syndrome.

Serum androgen binding capacity is decreased in hirsute women and normal women receiving medroxyprogesterone acetate. A sensitive radioimmunoassay was used to measure the main androgen binding protein, testosterone-estradiol-binding globulin, in 13 patients with hirsutism and the polycystic ovary syndrome. Testosterone-estradiol-binding globulin concentrations were determined before, during, and after treatment with medroxyprogesterone acetate. Testosterone-estradiol-binding globulin was lower in untreated polycystic ovary syndrome patients than in normal controls (21.9 +/- 3.7 versus 64 +/- 4 nmol/L, P less than .01). Administration of medroxyprogesterone acetate (400 mg intramuscularly every 15 days for nine months) to polycystic ovary syndrome patients caused a decrease of serum testosterone and further lowering of testosterone-estradiol-binding globulin (7.6 +/- 1.9 nmol/L, P less than .01). In two patients the concentration of testosterone-estradiol-binding globulin reached values as low as 0.9 and 0.8 nmol/L, approximately 1/60 and 1/70 of the normal level. Testosterone-estradiol-binding globulin returned to basal levels (15.1 +/- 1.3 nmol/L) between one and two years after discontinuation of medroxyprogesterone acetate. Corticosteroid binding globulin levels were normal in polycystic ovary syndrome and did not change with medroxyprogesterone acetate. It was concluded that: medroxyprogesterone acetate causes marked lowering of plasma testosterone-estradiol-binding globulin; the effect is not mediated by sex hormone levels; and the decrease in testosterone-estradiol-binding globulin offsets, at least partially, the beneficial action of medroxyprogesterone acetate.

Female↗
PubMed1986

Scintigraphic evidence of adrenal cortical dysfunction in the polycystic ovary syndrome.

The polycystic ovary syndrome (PCO) is frequently associated with elevated plasma levels of adrenal androgens and/or abnormal adrenal androgen responses to hormonal stimulation and suppression. Because of the overlap in the output of hormones between the adrenal glands and the ovaries, we measured adrenal iodocholesterol accumulation as an index of adrenocortical function in 11 women with PCO confirmed by laparoscopy or culdoscopy. All patients had normal dexamethasone suppression of plasma cortisol or urinary 17-hydroxycorticosteroid excretion. 6 beta-[131I]Iodomethylnorcholesterol (NP-59) adrenal scintiscans showed bilateral and excessive adrenal cortical uptake in PCO patients [0.46 +/- 0.08% (+/- SE) of the administered dose compared to 0.21 +/- 0.01% in a group of normal women; P less than 0.05]. The elevation of adrenal cortical NP-59 uptake in PCO was quantitatively similar to that in women with ACTH-dependent Cushing's syndrome (0.64 +/- 0.11%; P greater than 0.1). These data support the presence of abnormal adrenal cortical function in patients with PCO. The adrenal dysfunction of PCO most likely represents abnormal control of adrenal androgen production/secretion.

17-Hydroxycorticosteroids↗
PubMed1986

Primary hyperparathyroidism with low serum 1,25-dihydroxyvitamin D levels.

Primary hyperparathyroidism is usually associated with normal or elevated serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels. We report a patient with extreme hypercalcemia (serum calcium, 19.4 mg/dl), primary hyperparathyroidism, and a very low plasma concentration of 1,25-(OH)2D. Surgical removal of a large parathyroid adenoma was associated with a decrease in the serum calcium and immuno- and bioactive PTH concentrations and normalization of the 1,25-(OH)2D level. The postoperative course was complicated by severe protracted hypocalcemia and cardiac arrest, requiring treatment with large doses of calcium iv. The low concentrations of 1,25-(OH)2D in this patient are an unusual manifestation of primary hyperparathyroidism, probably due to suppression of renal 1 alpha-hydroxylase activity by the severe hypercalcemia. We conclude that in severe hypercalcemia, a low serum 1,25-(OH)2D level does not exclude the diagnosis of primary hyperparathyroidism.

Adenoma↗
PubMed1985

Renal and testicular agenesis in a patient with Darier's disease.

Darier's disease is a familial disorder of the skin that has been associated with corneal, bone, pulmonary, and urogenital abnormalities. This report describes a novel urogenital anomaly, namely renal and testicular agenesis, in a patient with Darier's disease. Detailed study of the kindred demonstrated an autosomal dominant pattern of inheritance for Darier's disease and also revealed the presence of autoimmune thyroiditis in several family members. Thyroid involvement ranged from isolated goiter to hypothyroidism. Tissue typing for HLA-A, B, C, and DR antigens did not reveal a specific haplotype common to all the carriers of the cutaneous or thyroid disorder. It is concluded that patients with Darier's disease should be carefully evaluated for the occurrence of systemic diseases, especially urogenital abnormalities and thyroid disorders.

Adolescent↗
PubMed1985

Macroprolactinemia presenting like a pituitary tumor.

A serum prolactin level greater than 200 ng/ml is almost pathognomonic of a pituitary tumor in a nonpregnant woman. A patient with a three-year history of documented serum prolactin levels of 350 to 400 ng/ml and no evidence of a pituitary adenoma on computed axial tomographic scanning was recently studied. Detailed evaluation included a 24-hour prolactin profile that revealed blunting of the nocturnal augmentation of prolactin release, low-dose dopamine infusion resulting in normal inhibition of prolactin secretion, and a thyrotropin-releasing hormone bolus that showed a blunted stimulation of prolactin release. Analysis of circulating prolactin by column chromatography of her serum revealed that greater than 85 percent of her circulating immunoreactive prolactin had a molecular weight greater than 100,000 daltons (macroprolactin). This contrasts with other hyperprolactinemic states in which 85 percent of the serum prolactin elutes in a 22,000-dalton peak. Hence, macroprolactinemia is apparently a nonprogressive condition and a novel cause of massive hyperprolactinemia.

Adult↗
PubMed1985

Characterization of a large molecular weight prolactin in women with idiopathic hyperprolactinemia and normal menses.

This study reports the presence of a large molecular sized PRL as the major form of circulating immunoactive PRL in five women with idiopathic hyperprolactinemia and normal menses. Gel filtration patterns of serum from these patients revealed 98-100% predominance of a 150,000- to 160,000-dalton PRL in contrast to the predominance of the 22,000-dalton species in other hyperprolactinemic patients. This 150,000- to 160,000-dalton PRL was immunologically similar to the 22,000-dalton PRL, and its size on gel filtration was not altered using denaturing conditions. With reduction of disulfide bonds, there was a shift of the peak I PRL to smaller mol wt peptides. In addition, studies of one woman with idiopathic hyperprolactinemia and normal menses revealed preservation of 98% peak I predominance during physiological and pharmacological perturbations of PRL secretion. Finally, assay of the bioactivity of the large molecular sized PRL in the Nb2 rat lymphoma line revealed diminished activity compared to the 22,000-dalton species. This latter finding may help explain the maintenance of normal menses and relative lack of clinical signs in patients with this form of hyperprolactinemia.

Adenoma↗
PubMed1985

gamma 3-Melanocyte-stimulating hormone immunoreactivity is a component of the neuroendocrine response to maximal stress (cardiac arrest).

The levels of gamma 3-MSH immunoreactivity (gamma 3MSH-IR), beta-endorphin immunoreactivity (beta-endorphin-IR), ACTH, PRL, and cortisol were determined in 23 patients with cardiac arrest (CA) and in a group of 22 patients consecutively admitted to the Intensive Care Unit (ICU controls). Blood was obtained immediately after CA and at frequent intervals for the next 2 h. In ICU patients, blood was obtained the morning after admission. gamma 3MSH-IR was consistently elevated after CA; it was present in all 23 patients and was detectable in 113 of 114 samples. The mean peak gamma 3MSH-IR level was 162 +/- 20 (+/- SE) pg/ml in CA patients and the mean gamma 3MSH-IR level was 35 +/- 6 pg/ml in ICU controls (P less than 0.01). gamma 3MSH-IR was undetectable (less than 20 pg/ml) in normal subjects. CA also was associated with increases in ACTH, beta-endorphin-IR, cortisol, and PRL. The group of ICU controls had stress hormone levels that were generally within the normal range. Distribution of plasma beta-endorphin-IR by gel chromatography showed two peaks of immunoreactivity corresponding to the beta-endorphin and beta-lipotropin standards in both the CA and ICU control groups. Distribution of gamma 3MSH-IR in CA plasma showed a major peak of immunoreactivity with a mol wt of approximately 6,000 daltons and two minor components of approximately 4,000 and 11,000 dalton. No immunoreactivity coeluted with a gamma 3MSH standard. We conclude that gamma 3MSH-immunoreactive peptides are a consistent component of the massive release of pituitary and adrenal glandular products after CA.

Adrenocorticotropic Hormone↗