Thyroid hormone extraction by plasma exchange: a study of extraction rate.

How to obtain an optimal efficiency of plasma exchanges in the treatment of severe hyperthyroidism has not been defined. In order to evaluate how long the exchanges must be continued to be fully effective in extracting thyroid hormones, we evaluated the extraction rate by repeated plasma sampling in two hyperthyroid patients and three euthyroid subjects who underwent a total of seven exchanges. Plasma concentrations of thyroid hormones were also determined just before, just after, and 24 hours following the exchange. The hormonal removal rate did not fall dramatically during the exchange, so that its efficiency--in terms of hormone extraction--depends closely on its duration. The determination of plasma thyroid hormone concentrations after the exchange does not appear to be useful in evaluating the thyroid hormone loss since these concentrations may not change in spite of the hormonal extraction.

Myxoedema coma: response of thyroid hormones with oral and intravenous high-dose L-thyroxine treatment.

Myxoedema coma is a medical emergency with high mortality. In this study, clinical response and plasma variations of thyroid hormones were analysed in 7 patients, 6 presenting with myxoedema coma and one with myxoedema ileus. These patients were treated with intravenous or oral l-thyroxine (l-T4). 1000 mu l-T4 iv were administered in two patients. Within 3 h, plasma T4 and triiodothyronine (T3) reached a peak upper normal range, then diminished slowly during 5-9 days. The 5 remaining patients were treated with 500 micrograms l-T4 po on the first day, then 100 micrograms l-T4 daily by mouth. Plasma T4 and T3 increased slowly, remaining in hypothyroid range but clinical response (assessed on mental status, pulse rate and body temperature) occurred within 24-72 h. Cortisone therapy was used in 3 patients. Two patients died of myocardial infarction, or septicemia, one while receiving cortisone therapy and i.v. l-T4, another one treated only by oral l-T4. This study suggests: 1) oral absorption of l-T4 is variable, but clinical response occurs quickly even in myxoedema ileus; 2) the intravenous route involves high peaks of plasma T4 and T3; 3) peripheral conversion of T4 to T3 allows gradually T3 delivery to organ systems, even if only l-T4 is used and 4) initial and daily dosage determinations need further studies.

Type 2 diabetes in the elderly: an assessment of metformin (metformin in the elderly).

Metformin efficacy and safety in type 2 diabetes has not been studied in the elderly patient under conditions pertaining to clinical practice. We have therefore, studied prospectively over two months 24 patients aged between 70-88 years with 115% mean ideal body wt and glycemic control greater than 10 mol.l-1 fasting and/or greater than 14 mol.l-1 postprandial, and/or an HbA1 value greater than 10%. At entry into the study, patients were on metformin + sulfonylurea (n = 15), sulfonylurea (n = 3), metformin (n = 2), insulin (n = 1) or diet alone (n = 3). They received metformin as the sole therapy when possible (sulfonylureas were discontinued in 9 cases) at a dosage of either 850 mg or 1,700 mg/day dependent on creatinine clearance values of 30-60 ml.min-1 (n = 11) and greater than 60 ml.min-1 (n = 13), respectively. Compared to pretreatment values, glycemic control at 1 and 2 months were unchanged, with metformin blood levels remaining within expected values for both dosage groups. Blood lactate levels remained unchanged in the high dosage group but were reduced (p less than 0.05) on 850 mg/day probably because of the reduction of metformin dosage in patients already treated prior to the study. It is concluded that provided the dosage is adjusted to renal function, the metabolic tolerance of metformin therapy is satisfactory in the elderly type 2 diabetic patient. With regard to efficacy, longer observations are needed to know whether this therapy may offer on a long-term basis equivalent glycemic control compared to other treatment modalities.

A case of pseudo-Nelson's syndrome: cure of ACTH hypersecretion by removal of a bronchial carcinoid tumor responsible for Cushing's syndrome.

It may sometimes be difficult to distinguish Cushing's disease from ectopic ACTH syndrome. A case is described here of a patient with a Cushing's syndrome and diagnostic difficulties. Initial features were consistent with a Cushing's disease (in particular metopirone test was positive). Because of relapse of hypercortisolism after mitotane therapy, total adrenalectomy was performed. Thereafter features occurred that evoked Nelson's syndrome, including high plasma ACTH levels and a pituitary mass syndrome. Pituitary reserve testings by vasopressin or corticotropin-releasing factor were positive, although inconstantly, in that plasma ACTH increased. A lung tumor was discovered about 20 yr after the first clinical signs of hypercortisolism. Its removal led to the discovery of a bronchial carcinoid tumor and was followed by normalization of plasma ACTH levels. An analysis of proopiomelanocortin-related peptides was performed postoperatively on the blood drawn before and after the tumor resection and on the tumor; the results of this study would have been contributive to the diagnosis of occult ectopic ACTH tumor. In conclusion this case demonstrates the limitations of the conventional procedures in the diagnosis of the ectopic ACTH syndrome. At contrast the newer biochemical procedures may be very useful in determining the type of hypercortisolism.

Hemodialysis in the treatment of lactic acidosis in diabetics treated by metformin: a study of metformin elimination.

The aim of this study was to determine the characteristics of metformin elimination by dialysis. For this purpose we report the kinetic parameters during dialysis and the metformin clearance (i.e. dialysance) in four patients presenting with lactic acidosis which occurred on metformin therapy. We also studied metformin elimination in two chronically hemodialyzed diabetic patients inadvertently maintained on metformin therapy and in two chronically hemodialyzed non-diabetic patients who took a single dose of metformin before a dialysis session. Analysis of plasma concentration-time curves showed a biphasic pattern of metformin - elimination, according to a two-compartment model. We demonstrate that metformin may be removed even after reaching an equilibrium between blood and dialysate levels in a recirculating system, suggesting a storage of metformin in a deep compartment with a gradient of concentration between this compartment and the blood. Lastly, metformin dialysance appears satisfactory (68 ml/min) even in the case of relatively low blood flow; this value reached 170 ml/min under good hemodynamic conditions. In conclusion, hemodialysis efficiently removes metformin and corrects metabolic acidosis in patients with metformin-induced lactic acidosis.

[Contraception for the diabetic woman]. / Contraception chez la femme diabetique.

PIP: Because of their vascular and metabolic risks for diabetic women, pregnancies must be carefully programmed to occur before the onset of degenerative diabetic manifestations. Diabetic women need an effective contraceptive method without undesirable side effects. The numerous side effects of combined oral contraceptives (OCs) are due to both the estrogens and progestins. Combined OCs have a diabetogenic effect whose mechanism is not clearly understood. Blood sugar levels are elevated under OCs and the insulin response is retarded and exaggerated. The number and affinity of insulin receptors are reduced. Norsteroid- derived progestins increase the state of insulin resistance. Combined OCs usually increase triglyceride levels. Changes in the level of high- density lipoprotein cholesterol under combined OCs vary with the estrogen and progestin content. Synthetic estrogens increase platelet aggregability, and blood pressure increases during OC use. Use of combined OCs represents increased vascular risk for diabetic women, with the risk of thrombosis multiplied by 4. Low dose progestin pills permit continued secretion of a small amount of luteinizing hormone and follicle stimulating hormone which may cause a relative hyperestrogenism and undesirable side effects. The secondary effects are often poorly tolerated. Use of this type of pill is limited except among diabetic women, 25% of whom are users. The failure rate is estimated at .2-2%. Standard-dosed norsteroids are unsuitable for diabetic women because of their metabolic and vascular side effects. 2nd and 3rd generation progestins have yielded more promising results. IUDs are used by about 12% of the overall female population but 32% of diabetic women, mostly multiparas, despite the increased risk of infection. Local methods have a higher failure rate and their success depends on patient compliance with instructions. 14% of diabetic women in a recent survey reported having undergone tubal ligation, which is not strictly speaking a contraceptive method. Combined OCs should be avoided in insulin- dependent diabetics because of their metabolic and vascular effects. Diabetic retinopathy should be added to the list of absolute contraindications to these methods. Low-dose progestins can be used in insulin-dependent diabetics or if they are poorly tolerated a standard dose pill can be substituted. IUD is the method of choice for older, multiparous insulin-dependent diabetics. Sterilization may be considered, especially if pregnancy is absolutely contraindicated. Combined OCs are formally contraindicated for noninsulin-dependent diabetics. Low-dose progestins could be tried. IUDs are suitable for multiparas.^ieng

Bicarbonate haemodialysis: an adequate treatment for lactic acidosis in diabetics treated by metformin.

Lactic acidosis in diabetics on metformin therapy is rare but still associated with poor prognosis. The authors report here five cases. Three patients were initially with a cardiovascular collapse and all had an acute renal failure. Sodium bicarbonate haemodialysis therapy led to a dramatic improvement. Consciousness and hemodynamic status recovered rapidly. Severe metabolic and blood gases derangements were also rapidly corrected. Plasma metformin removal, appreciated by repeated blood samplings in 3 cases, was satisfactory. All patients survived. However, blood metformin levels remained abnormally high at the end of the dialytic therapy. In conclusion, (1) bicarbonate dialysis is an adequate treatment of lactic acidosis observed in diabetic patients treated with metformin since it rapidly corrects the acid-base disorders and partially removes metformin; (2) the sole accumulation of metformin is not sufficient to explain lactic acidosis since this latter might be corrected in spite of persisting high levels of blood metformin.

Effect of thyrotoxicosis and its treatment on mineral and bone metabolism.

Mineral metabolism and bone histomorphometric status were evaluated in 31 hyperthyroid patients (HT) without clinical or radiological bone disease, both before and after treatment of hyperthyroidism. Blood and urine biochemical data were compared with those obtained in sex and age-matched controls. Iliac bone biopsies were available from 12 untreated HT and from 6 of them after treatment for analysis of trabecular bone. Mean plasma calcium was increased in HT but true hypercalcemia was seen in only one case and mean plasma immunoreactive parathormone (iPTH) was normal. Urine calcium excretion was markedly increased, especially in the fasting state. Biochemical parameters decreased after treatment, except for serum alkaline phosphatase and iPTH that, respectively, remained high and increased. Untreated state was characterized by an hyperremodelling state with enhanced activities of bone formation and bone resorption. Bone mineralization was normal. The mineral and bone changes were related to serum thyroid hormone levels. After treatment, the extent of formation surfaces still increased. The fact that, even though calcium metabolism abnormalities were corrected, active resorption surfaces did not change, suggests that trabecular osteoclastic resorption is not an important cause of mobilization of bone calcium to extracellular fluids in HT.

[Intrasellar carotid aneurysm simulating prolactin adenoma]. / Anévrysme de la carotide intrasellaire simulant un adénome à prolactine.

A 52-year-old woman with secondary amenorrhea presented with ophthalmoplegia, subarachnoidal bleeding. Pituitary function tests showed mild hyperprolactinemia and deficiencies of other functions of adenohypophysis. X-ray films of the skull showed enlarged sella turcica, and CT scan was interpreted as demonstrating pituitary tumour. Carotid arteriography led to diagnosis of intrasellar aneurysm of the right internal carotid, without any pituitary tumour. After embolisation of the aneurysm, followed, by a temporo-sylvian anastomosis, endocrine functions did not improve. The mechanism of hyperprolactinemia is discussed, probably due to pituitary ischemia. This case provides evidence of interest of further investigations before a transsphenoidal surgery in pituitary tumours, in particular if subarachnoidal bleeding occurs.

[Phospho-calcium and bone metabolism in hyperthyroidism in adults]. / Le métabolisme phospho-calcique et osseux au cours de l'hyperthyroïdie de l'adulte.

The abnormalities of calcium-phosphorum metabolism observed in hyperthyroidism (tendency to hypercalcaemia with subsequent functional hypoparathyroidism, increase in serum alkaline phosphatase and in hydroxyprolinuria) essentially result from excessive mobilization of bone calcium and phosphates by the thyroid hormones themselves. Histomorphometric studies have shown that the skeletal repercussions of hyperthyroidism are almost constant. There is, in particular, excessive bone remodelling due to increased bone-forming and bone-resorbing cellular activities. However, since bone resorption is quantitatively more stimulated than bone formation, the physiological bone loss is accelerated and is only partly repaired by re-establishment of the normal thyroid function.