[Thyroid dysfunction in pregnancy]. / Schilddrüsenfunktionsstörungen in der Schwangerschaft.

Thyroid dysfunction may impair fertility, course of pregnancy and fetal development. Physiological alterations of thyroid function parameters, that occur during pregnancy need to be distinguished from pathophysiological states of hypo- and hyperthyroidism. We performed a literature search (PubMed 1990-2013) and review relevant publications as well as consensus and practice guidelines of international thyroid/endocrine societies. Interpretation of thyroid function values in pregnancy must be based on trimester-specific TSH and T4 ranges. Alterations in thyroid function are present in up to 15% of pregnancies (0.4% overt hypothyroidism, 0.1-0.4% hyperthyroidism) and may lead to preventable complications in the pregnant woman and the fetus. Hypothyroidism is associated with an increased risk for abortion, premature delivery and stillbirth, besides impairment of neurocognitive development. The latter has also been shown in situations of grave iodine deficiency. In addition to new-born screening directed at early recognition of congenital hypothyroidism (incidence 0.03%), universal screening of all pregnant women should be implemented in health care guidelines. Newly diagnosed overt hypothyroidism in a pregnant woman requires immediate levothyroxine substitution at adequate doses. In subclinical hypothyroidism thyroid hormone replacement should be considered. Iodine supplementation is strongly recommended in all pregnant and breast-feeding women. Pregnancy causes a number of, that need to be of thyroid dysfunction. Both hypothyroidism and thyrotoxicosis may impair the course of pregnancy and may negatively affect the fetus. In particular, maternal hypothyroidism may lead to irreparable and detrimental deficits in the neurocognitive development of the fetus. Autoimmune thyroid disease is the most common cause of thyroid dysfunction in pregnancy. Hashimoto's thyroiditis is associated with impaired fertility and miscarriage, and may first manifest in pregnancy due to the increased thyroid hormone requirement. Graves' disease often shows a characteristic course in pregnancy with amelioration of thyrotoxicosis in the second half of pregnancy and exacerbation after delivery. In addition transplacental passage of maternal TSH receptor antibodies may lead to thyrotoxicosis in the fetus and/or newborn.

Diabetes insipidus as a rare cause of acute cognitive impairment in multiple sclerosis.

Multiple sclerosis (MS) is a complex neurodegenerative disease presenting with a diversity of clinical symptoms including palsy and cognitive impairment. We present a 59-year-old woman with a history of secondary progressive MS since 1987, who was referred to our department because of recent onset of confusion and polydipsia. Initial lab tests showed mildly elevated serum sodium levels and low urine osmolality. Under water deprivation, diuresis and low urine osmolality persisted and serum sodium levels rose above 150 mmol/l. Oral desmopressin resulted in normalisation of serum sodium as well as urine osmolarity, confirming a diagnosis of central diabetes insipidus. As drug-induced diabetes could be excluded, pituitary magnetic resonance imaging (MRI) was performed. A demyelinating lesion was detected in the hypothalamus. The patient was started on oral desmopressin treatment (0.2 mg/day). Fluid intake and serum sodium levels have since remained normal. In summary, we report the rare case of a patient presenting with diabetes insipidus due to progressive MS. Diabetes insipidus should be considered in MS patients who develop new onset of polydipsia.

[65-year old female patient with persistent hypercalcemia]. / 65-jährige Patientin mit persistierender Hyperkalzämie.

A 65-year old patient presented with newly diagnosed hypercalcemia and elevated parathyroid hormone levels. Exploration of parathyroid glands was performed under the diagnosis of primary hyperparathyroidism and was combined with thyreoidectomy due to concomittant multinodular goiter. However, no parathyroid adenoma was identified despite careful exploration. Therefore, the operation was terminated and an ectopic adenoma was suspected. A (99m)Tc-sestamibi scintigraphy with SPECT, neck ultrasound, neck CT scan with contrast media and selective venous sampling were performed for further localization of the adenoma. A single adenoma localized in the submandibular area of the left jaw was suspected and confirmed during surgical reexploration. Postoperatively, parathyroid hormone levels were below detection level and the patient required short-term calcium supplementation for symptomatic hypocalcemia.

Iodine nutrition, nodular thyroid disease, and urinary iodine excretion in a German university study population.

We determined the influence of different nutritional factors on the urinary iodine excretion in an East German university population. First, we assessed iodine excretion in spot urine samples. Second, we measured iodine content in the university canteen meals, where approximately 20% of the probands had regular meals. Third, we used a special food questionnaire to assess for other sources of nutritional iodine intake, namely iodine tablets, fish consumption, etc. Fourth, we determined the actual prevalence of goiter and thyroid nodules in our probands by high-resolution ultrasonography. The mean urinary iodine excretion in our cohort was 109 +/- 81 microg/g level indicating a borderline adequate iodine intake (100-200). The frequency of thyroid nodules was 30% and the frequency of goiter 11%. Thyroid volumes greater than 18 mL and 25 mL were considered to be enlarged in adult women and men respectively. Urinary iodine excretion was not related to the presence of goiter or thyroid nodules. In addition urinary iodine excretion did not vary with regular consumption of canteen meals, which contained approximately 50% of the daily recommended iodine intake. In contrast probands with regular supplementary intake of iodine tablets had significantly higher values of urinary iodine excretion (169 +/- 130 microg/g) compared to participants without (103 +/- 87 microg/g). No other single nutritional factor (e.g., salt, milk, or bread) had a statistically significant impact on urinary iodine excretion or was able to raise the urinary iodine excretion above the level of marginal iodine deficiency. In summary, the nutritional iodine intake in a Saxonian study population was found to be close to the margin of iodine deficiency. This shows insufficient supplementation of iodine through iodized salt/industrialized food production.

Autosomal dominant nonautoimmune hyperthyroidism. Clinical features-diagnosis-therapy.

Autosomal dominant nonautoimmune hyperthyroidism is a hereditary form of hyperthyroidism caused by constitutively activating germline mutations in the TSH-receptor gene. Clinical features comprise familial prevalence of thyroid autonomy in more than 2 generations and conditions of persisting neonatal hyperthyroidism or nonautoimmune hyperthyroidism of childhood onset with frequent relapses of hyperthyroidism under thyrostatic therapy and after thyroid surgery. Once clinically suspected the diagnosis can be confirmed by mutation analysis of genomic DNA extracted from a routinely obtainable EDTA blood sample. In patients with hereditary nonautoimmune hyperthyroidism a near total thyroidectomy is recommended as the first line treatment to avoid relapses from residual thyroid tissue with the activating TSHR mutation. Furthermore, genetic counselling of the affected patients is advised.

Acceleration of experimental diabetic retinopathy in the rat by omega-3 fatty acids.

Omega-3 fatty acids exert several important biological effects on factors that may predispose to diabetic retinopathy. Potential pathogenetic mechanisms include platelet dysfunction, altered eicosanoid production, increased blood viscosity in association with impaired cell deformability and pathologic leucocyte/endothelium interaction. Therefore, we tested whether a 6-month administration of fish oil (750 mg Maxepa, 5 times per week), containing 14% eicosapentaenoic acid (EPA) and 10% docosahexaenic acid, could inhibit the development of experimental retinopathy of the streptozotocin-diabetic rat. The efficiency of fish oil supplementation was evaluated by measuring EPA concentrations in total, plasma and membrane fatty acids and by measuring the generation of lipid mediators (leukotrienes and thromboxanes). Retinal digest preparations were quantitatively analysed for pericyte loss, and the formation of acellular capillaries. Omega-3 fatty acid administration to diabetic rats resulted in a twofold increase of EPA 20:5 in total fatty acids, and a reduction of the thromboxane ratio from 600 (untreated diabetic rats) to 50 (treated diabetic rats). Despite these biochemical changes, diabetes-associated pericyte loss remained unaffected and the formation of acellular, occluded capillaries was increased by 75% in the fish oil treated diabetic group (115.1 +/- 26.8; untreated diabetic 65.2 +/- 15.0 acellular capillary segments/mm2 of retinal area). We conclude from this study that dietary fish oil supplementation may be harmful for the diabetic microvasculature in the retina.

Omega-3 lipid infusion in a heart allotransplant model. Shift in fatty acid and lipid mediator profiles and prolongation of transplant survival.

BACKGROUND: omega-3 Fatty acids may have a major impact on immune responses involved in heart transplant rejection. We compared the effects of posttransplant intravenous supplementation with omega-3-rich versus omega-6-rich lipid emulsions on graft survival, plasma fatty acid profiles, and levels of arachidonic acid versus eicosapentaenoic acid-derived lipid mediators. METHODS AND RESULTS: Inbred PVG and Wistar-Kyoto rats were used as donors and recipients, respectively, in a model of heterotopic heart transplantation. Animals received 9 g/kg body wt per day of either fish oil-derived (n = 8) or soybean oil-derived fat (n = 7) in the form of a continuously infused lipid emulsion; controls were sham-infused with saline (n = 8). Graft rejection was assessed by loss of activity of the transplant. The fish oil-derived preparation but not that originating from soybean oil caused an increase in total and free plasma fatty acids. Substantial quantities of eicosapentaenoic acid and docosahexaenoic acid appeared in the free fatty acid fraction, surpassing those of arachidonic acid. Ex vivo stimulation of neutrophils with the Ca2+ ionophore A23187 demonstrated an increase in 5-series leukotriene (LT) generation in animals undergoing omega-3 lipid infusion (LTB5, omega-oxidation products of LTB5, LTA5 secretion), with 5-series/4-series LT ratios ranging between 0.08 and 0.36. Ratios of TX B3/B2 liberated from ex vivo stimulated platelets even approached 1:1 in omega-3 supplemented rats. Graft survival was 7.6 +/- 0.3 (mean +/- SEM) days in saline-infused, 10.4 +/- 0.7 in omega-6 lipid-infused, and 12.9 +/- 0.4 in omega-3 lipid-infused animals. CONCLUSIONS: Posttransplant intravenous alimentation with fish oil-derived lipid emulsions prolongs heart transplant survival in excess to omega-6 lipids. Profound changes in fatty acid profiles and lipid mediator generation may underlie this finding.

Influence of intravenous n-3 lipid supplementation on fatty acid profiles and lipid mediator generation in a patient with severe ulcerative colitis.

N-3 fatty acids were supplied to a 36-year-old female patient suffering from ulcerative colitis and severe steroid side-effects, in a sequence of parenteral and enteral administration. During a moderately active period of disease, 200 ml d-1 fish oil-derived lipid emulsion (eicosapentaenoic acid [EPA], 4.2 g; docosahexaenoic acid [DHA], 4.2 g) was infused for 9 days, in parallel with rapid tapering of the steroid dose. Disease activity declined rapidly, and the patient was subsequently provided with 16 fish oil capsules per day (EPA, 2.9 g; DHA, 1.9 g) for 2 months. At the end of this period of therapy, severe colitis recurred with intestinal and extraintestinal manifestations. The n-3 lipid emulsion was then used for intravenous alimentation (29 days, maximum dose 300 ml per day); during this time, marked improvement of the inflammatory bowel disease was noted. During both periods of parenteral n-3 lipid administration, total plasma EPA and DHA contents increased several-fold, surpassing that of arachidonic acid; this plasma n-3 fatty acid enrichment was only maintained to a minor extent during the intermediate period of dietary fish oil supplementation. The intravenously administered EPA-containing triglycerides were rapidly hydrolyzed, as evidenced by the appearance of substantial quantities of EPA in the plasma free fatty acid fraction. Platelet and neutrophil total membrane content of EPA and DHA as well as n-3 fatty acid/AA membrane ratios similarly increased during the periods of intravenous n-3 lipid administration and declined during oral fish oil uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

A double-blind, randomized, placebo-controlled trial of n-3 fatty acid based lipid infusion in acute, extended guttate psoriasis. Rapid improvement of clinical manifestations and changes in neutrophil leukotriene profile.

Twenty patients hospitalized for acute psoriasis guttata with a minimum 10% of body surface area involvement (range 10-90%) completed a 10-day trial in which they were randomly allocated to receive daily infusions with either an n-3 fatty acid based lipid emulsion [100 ml/day with 2.1 g eicosapentaenoic (EPA) and 21 g docosahexaenoic acid (DHA)] or a conventional n-6 lipid emulsion (EPA + DHA < 0.1 g/100 ml). The severity of disease was evaluated by scoring daily erythema, infiltration, and desquamation and by a subjective scoring of clinical manifestations offered by the patients. Leukotriene (LT) and platelet-activating factor (PAF) generation were investigated in ionophore-stimulated neutrophils obtained on days 0, 1, 3, 5, 10, and 40. Moderate improvement in clinical manifestations was noted in the n-6 group (changes in score systems between 16-25% from baseline within 10 days). In contrast, the severity of disease markedly decreased in all patients of the n-3 group, with improvements in all score systems ranging between 45% and 76% within 10 days (P < 0.05 for each variable). The difference in response to the two regimens was evident within 4-7 days after onset of lipid infusion. A more than ten fold increase in neutrophil EPA-derived 5-lipoxygenase product formation (LTB5, its omega-oxidation products, non-enzymatic degradation products of LTA5 and 5-hydroxyeicosapentaenoic acid) was noted in the n-3 group but not in the n-6 group. Neutrophil PAF generation increased in the n-6 group but decreased in the n-3 group. In conclusion, modulation of eicosanoid metabolism by intravenous n-3 fatty acid supplementation appears to exert a rapid beneficial effect on inflammatory skin lesions in acute guttate psoriasis.