Graves' Disease-Induced Psychosis Refractory to Intensive Medical Management Requiring Non-voluntary Thyroidectomy for Psychosis Resolution: A Case Report.

Graves' disease is an autoimmune disorder characterized by hyperthyroidism, ophthalmopathy, and dermatopathy. The chief thyroid hormone abnormality is the elevation of thyroid hormone, resulting in an overexcitation of the sympathetic and central nervous systems. Psychosis due to Graves' disease is rarely the first presenting symptom, but it is an essential complication of those with severe or untreated disease. Most patients respond well to standard medical management for Graves' disease, although there exists a small subset of people who do not. There are few cases describing patients with psychosis without underlying psychiatric disorders who require intensive care admission and thyroidectomy for necessary management of refractory psychosis secondary to thyrotoxicosis. Here, we present a case of a patient without medical or surgical history who presented with severe psychosis due to untreated Graves' disease requiring non-voluntary thyroidectomy for definitive management.

Lysine ingestion markedly attenuates the glucose response to ingested glucose without a change in insulin response.

BACKGROUND: Ingested proteins are known to stimulate a rise in insulin and glucagon concentrations. In our effort to explain this effect, we have begun to measure the effect of individual amino acids. OBJECTIVES: The objectives were to determine the effect of lysine ingestion on insulin and glucagon concentrations and whether the effect is moderated by glucose ingestion. DESIGN: Thirteen healthy subjects were studied on 4 occasions. Water, 25 g glucose, 1 mmol lysine/kg lean body mass, or lysine plus glucose was given on separate occasions at 0800 after a 12-h fast. Serum lysine, glucose, insulin, and glucagon were measured during a 2.5-h period. The amount of lysine provided was equivalent to that present in a 672-g (24-oz) steak. RESULTS: Lysine ingestion resulted in an approximately 3-fold increase in lysine concentration and in a small decrease in glucose concentration. When lysine was ingested with glucose, the 2.5-h glucose area response decreased by 44% (P < 0.02). Lysine alone increased the insulin area response modestly; the insulin increase when lysine was ingested with glucose was similar to that when only glucose was ingested. Lysine stimulated an increase in glucagon (P < 0.02), whereas glucose decreased glucagon. CONCLUSIONS: Lysine ingestion results in a small decrease in serum glucose and an increase in glucagon and insulin concentrations. Lysine ingested with glucose dramatically attenuated the glucose-stimulated glucose response, but there was no change in insulin response. Whether similar effects will be observed with more physiologic doses of lysine remains to be determined.

Leucine, when ingested with glucose, synergistically stimulates insulin secretion and lowers blood glucose.

Our laboratory is interested in the metabolic effects of ingested proteins. As part of this research, we currently are investigating the metabolic effects of ingested individual amino acids. The objective of the current study was to determine whether leucine stimulates insulin and/or glucagon secretion and whether, when it is ingested with glucose, it modifies the glucose, insulin, or glucagon response. Thirteen healthy subjects (6 men and 7 women) were studied on 4 different occasions. Subjects were admitted to the special diagnostic and treatment unit after a 12-hour fast. They received test meals at 8:00 am. On the first occasion, they received water only. Thereafter, they received 25 g glucose or 1 mmol/kg lean body mass leucine or 1 mmol/kg lean body mass leucine plus 25 g glucose in random order. Serum leucine, glucose, insulin, glucagon, and alpha-amino nitrogen concentrations were measured at various times during a 2.5-hour period after ingestion of the test meal. The amount of leucine provided was equivalent to that present in a high-protein meal, that is, that approximately present in a 350-g steak. After leucine ingestion, the leucine concentration increased 7-fold; and the alpha-amino nitrogen concentration increased by 16%. Ingested leucine did not affect the serum glucose concentration. When leucine was ingested with glucose, it reduced the 2.5-hour glucose area response by 50%. Leucine, when ingested alone, increased the serum insulin area response modestly. However, it increased the insulin area response to glucose by an additional 66%; that is, it almost doubled the response. Ingested leucine stimulated an increase in glucagon. Ingested glucose decreased it. When ingested together, the net effect was essentially no change in glucagon area. In summary, leucine at a dose equivalent to that present in a high-protein meal, had little effect on serum glucose or insulin concentrations but did increase the glucagon concentration. When leucine was ingested with glucose, it attenuated the serum glucose response and strongly stimulated additional insulin secretion. Leucine also attenuated the decrease in glucagon expected when glucose alone is ingested. The data suggest that a rise in glucose concentration is necessary for leucine to stimulate significant insulin secretion. This in turn reduces the glucose response to ingested glucose.

S14: insights from knockout mice.

Spot 14 (S14) is a protein whose mRNA is rapidly up-regulated by lipogenic stimuli including thyroid hormone and a high-carbohydrate diet. Previous investigation into the role of S14 suggested that it is involved in de novo lipogenesis. Knockout of the gene in mice has given further support to this hypothesis. The lack of S14 in different tissues resulted in varying phenotypic effects. In the lactating mammary gland, levels of lipogenesis, specifically the production of medium chain fatty acids, were decreased, whereas hepatic lipogenesis was not decreased. In fact, hepatic lipogenesis was increased, and the increase may be due to compensation by a paralog of S14 called S14-R. S14-R is expressed in the liver but not the mammary gland. Importantly, S14 knockout mice did not have reduced levels of lipogenic enzymes, implying that it does not affect the transcriptional rate of those enzymes. Instead, S14 may act in the cytoplasm to affect lipogenesis.