Metastatic pure papillary thyroid carcinoma presenting as a toxic hot nodule.

In the majority of cases, carcinoma of the thyroid presents as a cold nodule by radioiodine and Tc-99m sodium pertechnetate scintigraphy. Whereas the presence of a hot nodule usually implies a benign entity, it does not provide complete assurance against thyroid malignancy. Presented is a rare case of metastatic pure papillary thyroid carcinoma appearing as a hot nodule on Tc-99m sodium pertechnetate and I-123 sodium iodide scintigraphy. The implications of such a case, its management, and review of the pertinent literature are discussed.

Unusual manifestations of cushing's syndrome in a multiple endocrine neoplasia type I kindred.

OBJECTIVE: To describe two unusual cases of Cushing's syndrome in a kindred with multiple endocrine neoplasia type I (MEN I). METHODS: The clinical and laboratory data as well as follow-up course of the two patients are reviewed in detail. RESULTS: Our first patient with a history of MEN I had hypercortisolism and computed tomographic evidence of a right adrenal mass (8.5 by 11 cm) extending into the inferior vena cava as well as multiple pulmonary nodules. He was diagnosed with Cushing's syndrome attributable to metastatic adrenal cancer that progressed despite chemotherapy. He died 2 years later. His son, who was also diagnosed with MEN I, had adrenocorticotropic hormone-dependent Cushing's syndrome. The plasma corticotropin-releasing hormone (CRH) level was high; magnetic resonance imaging showed normal pituitary findings but an islet cell tumor of the pancreas. The islet cell tumor was resected, and the patient's urinary cortisol declined to upper limits of normal. CRH was detected in the tissue, and the patient was thought to have Cushing's syndrome as a result of a CRH-secreting islet cell tumor. One year later, however, his Cushing's syndrome recurred. Inferior petrosal sinus sampling suggested a pituitary source, and the patient underwent transsphenoidal hypophysectomy. Histopathologic examination did not reveal pituitary hyperplasia or microadenoma, but the patient was cured of his Cushing's syndrome. CONCLUSION: Cushing's syndrome is a rare initial manifestation of MEN I. We report two unusual causes of Cushing's syndrome in MEN I--that is, adrenal cancer and a probable CRH-secreting islet cell tumor. The natural history of Cushing's syndrome in MEN I is not known; further studies should be conducted.

Both hypothyroidism and hyperthyroidism enhance low density lipoprotein oxidation.

Hypothyroidism is frequently associated with hypercholesterolemia and an increased risk for atherosclerosis, whereas hyperthyroidism is known to precipitate angina or myocardial infarction in patients with underlying coronary heart disease. We have shown previously that L-T4 functions as an antioxidant in vitro and inhibits low density lipoprotein (LDL) oxidation in a dose-dependent fashion. The present study was designed to evaluate the changes in LDL oxidation in subjects with hypothyroidism and hyperthyroidism. Fasting blood samples for LDL oxidation analyses, lipoprotein determinations, and thyroid function tests were collected at baseline and after the patients were rendered euthyroid. The lag phase (mean +/- SEM hours) of the Cu+2-catalyzed LDL oxidation in the hypothyroid state and the subsequent euthyroid states were 4 +/- 0.0.65 and 14 +/- 0.68 h, respectively (P < 0.05). The lag phase during the hyperthyroid phase was 6 +/- 0.55 h, and that during the euthyroid phase was 12 +/- 0.66 h (P < 0.05). The total and LDL cholesterol levels were higher in hypothyroidism than in euthyroidism and were lower in hyperthyroidism than in the euthyroid state. We conclude that LDL has more susceptibility to oxidation in both the hypothyroid and hyperthyroid states. Thus, the enhanced LDL oxidation may play a role in the cardiac disease process in both hypothyroidism and hyperthyroidism.

Inhibition of low-density lipoprotein oxidation by oral herbal mixtures Maharishi Amrit Kalash-4 and Maharishi Amrit Kalash-5 in hyperlipidemic patients.

Low-density lipoprotein (LDL) oxidation is central to the pathogenesis of atherosclerosis. We have shown previously that the herbal mixtures Maharishi Amrit Kalash-4 (MAK-4) and Maharishi Amrit Kalash-5 (MAK-5) inhibit LDL oxidation induced by cupric ions (Cu+2) and endothelial cells in vitro and that MAK-4 reduces atherosclerosis in Watanabe heritable hyperlipidemic rabbits that were fed this herbal mixture. This study evaluates the antioxidant activity of MAK-4 and MAK-5 in vivo. Ten hyperlipidemic patients prescribed stable hypolipidemic therapy were treated with MAK-4 and MAK-5 for 18 weeks. Plasma lipoprotein, plasma lipid peroxide, and LDL oxidation studies were performed every 6 weeks. Apolipoprotein A, apolipoprotein B, and lipoprotein (a) levels were measured at baseline and 18 weeks. After 12 weeks of treatment with MAK-4 and MAK-5, a time-dependent increase in the lag phase and delay in the propagation phase of oxidation of LDL by Cu+2 and endothelial cells was seen. Lag phases at baseline and after 6, 12, and 18 weeks of MAK-4 and MAK-5 ingestion were 6.66 hours +/- 0.19 (mean +/- standard error of mean), 6.77 hours +/- 0.31, 7.22 hours +/- 0.24, and 18.00 hours +/- 0.73, respectively, for Cu(+2)-catalyzed LDL oxidation. Lag phases were 14.89 hours +/- 0.77, 13.33 hours +/- 0.50, 20.22 hours +/- 0.76, and 20.00 hours +/- 0.79, respectively, for endothelial cell-induced LDL oxidation. The levels of plasma lipid peroxide did not change significantly. No significant changes were seen in the plasma lipoproteins and the levels of apolipoprotein A, apolipoprotein B, and lipoprotein (a). The results show that MAK-4 and MAK-5 inhibit LDL oxidation in patients with hyperlipidemia. Therefore, MAK-4 and MAK-5 may be useful in the prevention and treatment of atherosclerosis.

RET mutation screening in MEN2 patients and discovery of a novel mutation in a sporadic medullary thyroid carcinoma.

RET germline mutations were found to predispose to the development of three variants of multiple endocrine neoplasia type 2, MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC). We have screened for RET mutations at exons 10, 11, 13, and 16 in leukocyte DNA extracted from 37 individuals, and have identified RET germline mutations in 12 affected individuals from 9 unrelated families. No RET germline mutation was found in 19 individuals with apparent sporadic diseases. We have also screened for RET mutations at exons 10, 11, and 16 in tumor DNA extracted from 13 freshly frozen medullary thyroid carcinomas (MTC). RET mutation was detected in every tumor, either inherited or sporadic, indicating that RET plays an important role in the development of both inherited and sporadic MTC. We initially screened for RET mutations by direct DNA sequencing of the genomic PCR products amplified from patients' leukocyte or tumor DNA. Recently, we utilized the "Cold SSCP" method, nonradioactive single-stranded conformation polymorphism analysis, to screen for RET mutations and have identified a novel mutation, a 6-bp deletion preceding the cysteine-634, in a sporadic MTC.

Fibrosing pseudotumor of the sella and parasellar area producing hypopituitarism and multiple cranial nerve palsies.

We present an unusual patient with a medical history of a fibrosing pseudotumor of the left orbit that had been stable for 8 years who presented with acute anterior hypophyseal failure. During the next 10-month period, sequential magnetic resonance scans showed a rapid growth of a plaque-like sellar and parasellar mass extending into the right cavernous sinus, right Meckel's cave, along the dural surfaces of the clivus, dens, and body of the second cervical vertebra. A transsphenoidal biopsy revealed sphenoid and intrasellar pseudotumor that invaded the adenohypophysis and had microscopic features identical to those of the previously excised orbital pseudotumor. Rapid growth of the pseudotumor continued despite a course of radiotherapy. Palsies of cranial nerves V and VI and of the sensory root of the cranial nerve VII developed on the right side. Steroid therapy was associated with improvement of the cranial nerve palsies. This is the first report of the sellar fibrosing pseudotumor producing not only anterior hypophyseal failure, but also cranial nerve dysfunction secondary to plaque-like extension into the cavernous sinus, Meckel's cave, and cranial base dura. This intracranial plaque-like extension of a fibrous pseudotumor corresponds to a hypertrophic intracranial pachymeningitis, which is a rare, previously described phenomenon associated to the syndrome of multifocal fibrosclerosis.

The use of continuous subcutaneous octreotide infusion in brittle type 1 diabetic patients.

Two Type 1 diabetic patients with brittle diabetes were successfully treated using continuous SC octreotide (Sandostatin) infusion (200 micrograms 24-h-1) for 6 months and 12 months. When the analogue was discontinued, rapid deterioration in glucose control and ketonuria recurred in one patient and diabetic ketoacidosis in the other. These were corrected after reinstitution of the analogue.

17 alpha-hydroxylase deficiency masquerading as primary hyperaldosteronism.

A unique case of 17 alpha-hydroxylase deficiency with steroid-responsive primary hyperaldosteronism is reported. Initially the patient was misdiagnosed as testicular feminization for 16 years and was thought to have typical primary hyperaldosteronism for 5 years. However, careful detailed endocrine studies showed markedly elevated progesterone, deoxycorticosterone, and 18-hydroxycorticosterone values with low levels of 17-hydroxyprogesterone, 11-deoxycortisol, testosterone, and DHEA-Sulfate. In contrast to the suppressed aldosterone levels that are found in 17 alpha-hydroxylase deficiency, this patient's aldosterone levels were inappropriately elevated before and after ACTH stimulation. Use of glucocorticoid replacement resolved the patient's symptoms and completely corrected the hypokalemia and hypertension. In summary, recognition of 17 alpha-hydroxylase deficiency with steroid-responsive primary hyperaldosteronism is important because hypertension, hypokalemia, and symptoms respond to steroid replacement.

Metastatic pheochromocytoma associated with multiple endocrine neoplasia syndrome type II.

Pheochromocytoma is a rare adrenal medullary tumor of chromaffin cell origin that presents a syndrome of alpha- and beta-adrenergic receptor stimulation due to secretion of epinephrine and norepinephrine. This tumor occurs sporadically in the population and is also associated with multiple endocrine neoplasia syndrome type II (MEN II). Although malignant pheochromocytoma is associated with sporadic tumors, those associated with familial MEN syndromes are rarely malignant. We report a case of a rare metastatic pheochromocytoma in a patient with MEN IIA. Surgical debulking, which has been shown to benefit many patients with metastatic neuroendocrine tumors, was attempted in this patient. Palliation, with symptom relief, was provided. The options for treatment of metastatic pheochromocytoma are discussed.

Lipoprotein analyses in varying degrees of glucose tolerance. Comparison between non-insulin-dependent diabetic, impaired glucose tolerant, and control populations.

Atherosclerosis is the major cause of death in diabetic patients. Lipoproteins and lipids are frequently altered in non-insulin-dependent diabetes. These lipoprotein alterations are of interest because of their possible role in the origin of the accelerated atherosclerosis found in diabetes. Because of the link between lipoproteins and diabetes, serum lipids and lipoproteins were measured in 215 middle-aged patients (107 female, 108 male) with varying degrees of glucose tolerance: control subjects, subjects with impaired glucose tolerance (IGT), and patients with non-insulin-dependent diabetes mellitus (NIDDM). In male subjects, levels of fasting total triglycerides were significantly greater in those with NIDDM compared with control subjects. In female subjects, fasting total cholesterol levels were significantly greater in NIDDM compared with IGT. Both high-density lipoprotein (HDL) cholesterol and HDL2 cholesterol values were significantly lower in both sexes with NIDDM compared with control subjects. Low-density lipoprotein (LDL) cholesterol levels were elevated in the male subjects with IGT. No differences in HDL cholesterol or its subfractions were seen in both sexes with IGT compared with control subjects. Bivariate analyses showed that the reduced HDL cholesterol and HDL subfraction levels were most closely associated with both total triglycerides and weight. This study shows that reduced HDL cholesterol and HDL2 cholesterol levels occur in NIDDM, whereas persons with "impaired glucose tolerance" do not have the dramatic alterations in HDL levels.

Metoclopramide suppositories in the treatment of diabetic gastroparesis.

Gastroparesis diabeticorum is a common complication that develops in patients with diabetes mellitus. Although the pathogenesis remains unclear, the clinical symptoms of nausea, vomiting, and gastric dilatation frequently respond to metoclopramide hydrochloride, an agent that stimulates gastric emptying in addition to acting centrally as an antiemetic. Occasionally, patients are encountered whose severe gastroparesis is unresponsive to oral metoclopramide and who require intravenous therapy or drainage procedures (eg, pyloroplasty or gastrojejunostomy). Rectal administration of metoclopramide successfully controlled the clinical symptoms of gastroparesis diabeticorum in an outpatient after failure of oral dosing, thus avoiding the need for intravenous therapy. Gastric emptying studies and serum metoclopramide levels following a 25-mg rectal dose of metoclopramide hydrochloride verified the efficacy of therapy.

Indapamide. Effects on apoprotein, lipoprotein, and glucoregulation in ambulatory diabetic patients.

We evaluated the long-term effects of indapamide, a non-thiazide diuretic, on blood pressure, glucoregulation, free insulin and C-peptide levels, and lipoprotein and apoprotein metabolism in 13 hypertensive diabetic patients for 24 weeks. Indapamide significantly reduced both systolic and diastolic blood pressure by 15% and 17%, respectively. Both mean fasting serum glucose and integrated glucose responses after oral glucose load (75 g) were significantly higher during indapamide therapy than at week 0. The mean fasting and stimulated C-peptide responses were significantly increased despite worsening glucose control. At the end of 24 weeks, mean glycosylated hemoglobin level had increased significantly. Indapamide caused a slight but insignificant rise in the total triglyceride, cholesterol, and low-density lipoprotein cholesterol levels, while the high-density lipoprotein cholesterol level decreased. In addition, the apoprotein A-1 concentrations remained unchanged while the apoprotein B-100 level decreased. Apart from hypokalemia (less than 3.5 mEq/L [less than 3.5 mmol/L]) in three patients that required oral potassium supplementation, biochemical changes were of no clinical consequence.

Coexistence of diabetes mellitus, optic atrophy, and sensorineural deafness: case report.

The association of diabetes mellitus, optic nerve atrophy, and sensorineural deafness is a rare but distinct syndrome. We describe an 18-year-old woman who developed diabetes mellitus at three years of age, sensorineural deafness at 14 years of age, and bilateral asymptomatic optic atrophy at 18 years of age. Diabetic retinopathy was notably absent. Forty-two patients with diabetes mellitus and optic atrophy have been described. All had type I diabetes mellitus without typical diabetic retinopathy even though insulin-dependent diabetes mellitus was present for many years. Other neurologic abnormalities, including diabetes insipidus, epilepsy, and nystagmus, have been described in association with diabetes mellitus and optic atrophy. A distinct, heredofamilial genetic mechanism, unrelated to diabetes mellitus per se, is postulated.

Chronic hyponatremia associated with diabetic amyotrophy.

In most diabetic patients, the presence of hyponatremia is usually ascribed to severe hyperglycemia, hypertriglyceridemia, oral hypoglycemic agents, or other drugs. We describe two insulin-treated type II diabetic patients who were seen with severe rapid weight loss, hyponatremia, and diabetic amyotrophy despite good metabolic control. Laboratory evaluation of the hyponatremia suggested the syndrome of inappropriate antidiuretic hormone secretion. Their clinical presentations led to the suspicion of an underlying malignant neoplasm in each case. One patient required demeclocycline for treatment of his symptomatic hyponatremia, while the other improved with fluid restriction and intermittent furosemide therapy. The hyponatremia resolved spontaneously with improvement in body weight and the amyotrophy resolved after four to six months. After 24 to 36 months of close follow-up, no evidence of malignancy has been documented in either of the patients. We conclude that this clinical entity of amyotrophy is benign and should be included in the differential diagnosis of chronic hyponatremia in diabetic patients.

The effects of carbohydrate-enriched meals on glucose turnover and metabolic clearance rates of glucose in type 2 diabetic patients.

The addition of fructose to natural meals elicits lower serum glucose and immunoreactive insulin responses when compared with that of sucrose and starch meals. Differences in rates of splanchnic glucose appearance and peripheral glucose disposal may be partly responsible. To evaluate the role of both parameters after different carbohydrate-enriched meals, we measured the arterialized venous blood glucose, immunoreactive insulin and gastric inhibitory polypeptide concentrations in seven Type 2 diabetic patients after ingestion of isocaloric test meals. Measurements were made in a random manner on three separate occasions. Fructose, sucrose, and bread supplementation constituted 68% of the total carbohydrate content of each meal. Rates of total glucose appearance, glucose utilization and metabolic clearance rates of glucose were determined by the D3-H-3 glucose prime-continuous infusion technique. The mean fasting glucose levels were similar in the three groups. Mean peak glucose concentrations and integrated incremental areas were significantly lower (p less than 0.02) after the fructose-enriched meals compared with that of either sucrose or bread. The basal arterialized venous blood glucose levels were similar in all three groups. The mean incremental integrated arterialized venous blood glucose area was significantly lower in the fructose group when compared with the sucrose (p less than 0.05) and bread (p less than 0.02) groups. The mean fasting gastric inhibitory polypeptide levels were similar in the three groups. However, the mean incremental integrated gastric inhibitory polypeptide areas were significantly lower in the fructose group compared with the sucrose and bread groups (p less than 0.01 and p less than 0.05 respectively). Basal hepatic glucose outputs were not significantly different in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastric inhibitory polypeptide responses and glucose turnover rates after natural meals in type II diabetic patients.

Gastric inhibitory polypeptide (GIP) has insulinotropic actions in the presence of hyperglycemia. However, its extrapancreatic effects on glucose homeostasis are controversial. We have studied the relationships between GIP and immunoreactive insulin (IRI) and glucose turnover rates (D3H-3 glucose technique) in five poorly controlled type II diabetic patients and five normal subjects before and after a breakfast containing 500 kcal including 42 g sucrose. Mean fasting serum glucose levels and glucose responses were significantly (P less than 0.001) higher in the diabetic patients than in normal subjects. Mean basal serum IRI levels were similar in both groups [12.8 +/- 2.9 (SEM) vs. 11.8 +/- 2 microU/ml, P = NS]. After meal ingestion, mean IRI levels rose significantly to a peak at 20 min in the normal subjects but the responses were blunted in the diabetic patients (74 +/- 10 vs. 24 +/- 6 microU/ml, P less than 0.001). At all other times studied (60-180 min), mean serum IRI levels were similar in the diabetic patients and the normal subjects except at 180 min. Mean basal serum GIP levels were similar in the diabetic patients and the normal subjects (538 +/- 100 vs. 400 +/- 50 pg/ml, P = NS). After meal ingestion, mean GIP levels rose between 0-60 min but were significantly higher in the diabetic patients only at 20 min (1200 +/- 190 vs. 566 +/- 76 pg/ml, P less than 0.01). Mean basal hepatic glucose output was higher (P less than 0.01) in the diabetic patients. However, the mean basal MCR values were similar. After meal ingestion, total splanchnic glucose output and rates of glucose utilization (RU) were significantly higher in the diabetic patients compared with the normal subjects (P less than 0.001, and P less than 0.001, respectively). Postmeal MCR values were not statistically different in both groups. There were significant positive correlations between postmeal splanchnic glucose output and both IRI (r = 0.805, P less than 0.005) and GIP (r = 0.749, P less than 0.02) in the diabetic patients but not in the normal subjects (r = 0.10, P = NS for both). Whereas no relationships existed between RU and IRI in either group, RU correlated strongly with GIP (r = 0.810, P less than 0.005) only in the diabetic patients. We hypothesize that GIP may play a compensatory role to improve both impaired beta-cell insulin release and peripheral glucose utilization which are the recognized pathogenetic mechanisms underlying type II diabetes mellitus.

Premenstrual syndrome: concerns, controversies, and treatment.

Premenstrual syndrome is of interest to health care professionals today because of media attention and large numbers of women who are concerned about their premenstrual symptoms. At the same time, there is a lack of consensus as to diagnostic criteria and specific treatment. There appears to be a relationship between mood disorders such as major depression and luteal phase symptoms. An approach to the diagnosis and treatment of the patient with premenstrual syndrome is described.

Iodine-131 labeled anti-CEA antibodies uptake by Hürthle cell carcinoma.

Localization of Hürthle cell cancer deposits in the lung with I-131 labeled anti-carcinoembryonic antigen (CEA) monoclonal antibody is described. This technique may prove useful if conventional scanning with I-131 sodium iodide for distant metastases is negative.