Thyroid function and pregnancy: before, during and beyond.

Thyroid disturbances are common in women during the reproductive years of their lives. Autoimmunity and altered iodine status together account for a high proportion of the abnormalities. Autoimmune thyroid disease is present in around 4% of young females, and up to 15% are at risk because they are thyroid antibody-positive. There is a strong relationship between thyroid immunity on the one hand and infertility, miscarriage, and thyroid disturbances in pregnancy and postpartum on the other hand. Suboptimal iodine status affects a large proportion of the world's population, and pregnancy further depletes iodine stores. There is controversy surrounding the degree to which iodine should be supplemented and the duration of supplementation. Recent studies have helped to clarify the relationship between maternal thyroid status and neuropsychological development of the child. The role of other environmental factors including smoking and selenium status is also now recognised. Universal screening for thyroid hormone abnormalities is not routinely recommended at present. However, measurement of thyroid function and autoantibodies should certainly be considered in those who are at high risk of thyroid disease and in those whose pregnancy is otherwise high risk. The practicing clinician needs to be aware of the thyroid changes which accompany pregnancy.

Prognostic value of postoperative and post-ablative serum thyroglobulin levels in patients with differentiated thyroid cancer.

BACKGROUND: The study was designed to examine the value of post-operative and post-ablative serum thyroglobulin levels and diagnostic whole body scan in predicting remission in patients with differentiated thyroid carcinoma. METHODOLOGY: Serum TG levels and diagnostic iodine-123 whole body scans performed prior to and 6-12 months after 131I ablation for DTC were evaluated in 100 consecutive patients at King Faisal Specialist Hospital Riyadh. Patients were followed up for a period of 7.6 years (range 7-10 years). All patients underwent total thyroidectomypriorto 131I ablation. RESULTS: Patients with serum TG levels < 8 ng/ml post thyroidectomy (50 patients) also maintained low TG < 8 ng/ml after 131I ablation and had better outcome (60%) remission. On the other hand DTC subjects with higher TG > 8 ng/ml post thyroidectomy (50 patients) 40% remained in remission X2 = 4.00, p = 0.046. For the group with initial high post-operative TG, it became < 8 ng/ml in 34/50 (68%) patients after ablation with 131I and in this subgroup, remission was seen in 16/34 (47%) of patients in contrast to 4/16 (25%) remission rate in those who continue to have TG > 8 ng/ml after ablation. At the end of follow up, 123I-WBS was positive in 4% and 10% of patients with initial TG < 8 ng/ml and TG > 8 ng/ml respectively; X2 = 1.38, p= 0.24. CONCLUSION: Post-operative and post-ablative serum TG levels -but not follow up diagnostic WBS- have predictive values and permit selection of patients with higher risk for persistent/recurrent disease.

Insulinoma in Saudi Arabia: a twenty-year hospital study.

The study was designed to assess retrospectively clinical pattern of insulinoma at a national referral center in the Kingdom of Saudi Arabia. All cases of insulinoma recorded at King Khalid University Hospital Riyadh between January 1987 and December 2006 were reviewed. During the 20-year period five patients were seen comprising three females (ages 38, 40, and 70 years) and two males (17 and 34 years). The duration of symptoms prior to diagnosis ranged between one and eight years. The commonest mode of presentation before diagnosis was inability to observe Ramadan fasting. Other notable symptoms included dizziness and loss of consciousness. All the five patients proceeded to operation. At surgery all were found to be benign tumors. Post-operatively, three of the patients developed pseudocyst, which resolved upon undergoing second surgery. Though clinical presentation of insulinoma in Saudi subjects is similar to those reported in the literature, our study revealed prominent symptoms occurring during yearly ramadan religious fast could be a useful information in history taking. Further studies on a larger population are needed to further characterize our findings.

Insulinoma in Saudi Arabia: a twenty-year hospital study.

The study was designed to assess retrospectively clinical pattern of insulinoma at a national referral center in the Kingdom of Saudi Arabia. All cases of insulinoma recorded at King Khalid University Hospital Riyadh between January 1987 and December 2006 were reviewed. During the 20-year period five patients were seen comprising three females (ages 38, 40, and 70 years) and two males (17 and 34 years). The duration of symptoms prior to diagnosis ranged between one and eight years. The commonest mode of presentation before diagnosis was inability to observe Ramadan fasting. Other notable symptoms included dizziness and loss of consciousness. All the five patients proceeded to operation. At surgery all were found to be benign tumors. Post-operatively, three of the patients developed pseudocyst, which resolved upon undergoing second surgery. Though clinical presentation of insulinoma in Saudi subjects is similar to those reported in the literature, our study revealed prominent symptoms occurring during yearly ramadan religious fast could be a useful information in history taking. Further studies on a larger population are needed to further characterize our findings.

Diabetic foot osteomyelitis: usefulness of erythrocyte sedimentation rate in its diagnosis.

BACKGROUND: Recently, ESR was reported to have a useful diagnostic value in detecting diabetic osteomyelitis. The test has been performed in a limited number of patients. This laboratory parameter is simple and could be routinely performed in developing countries where diabetes and its complication are increasingly being encountered. OBJECTIVE: To evaluate the reliability of erythrocyte sedimentation rate (ESR) in differentiating diabetic osteomyelitis from cellulitis, and to compare its diagnostic value with other hematological indices. METHODS: In a one-year prospective study, forty -three adult diabetic patients with foot ulcers were assessed at King Abdulaziz University Hospital Diabetes Center Riyadh from 1st January to 31st December 2005. ESR was compared with other hematological profiles in differentiating osteomyelitis from cellulitis. RESULTS: ESR, white blood cell count (WBC), platelet count, and red cell distribution width (RDW) were higher in patients with osteomyelitis than in patients with cellulitis (p<0.0001 for ESR; others p<0.05). In contrast, haematocrit and haemoglobin levels were lower in patients with osteomyelitis than in patients with cellulitis (p<0.0001). Overall, the efficiency of the haematological parameters in correctly diagnosing diabetic osteomyelitis from cellulitis was highest for ESR > 70 mm/hr (92%), followed by haematocrit < 36% (89%), haemoglobin < 12 g/dl (85%), platelet count > 400x10(9) (69%), RDW > 14.5 (65%), and WBC >11x10(9) (63%). CONCLUSION: It is concluded that of the haematological parameters, ESR has the best diagnostic discrimination between diabetic foot osteomyelitis from cellulitis. Further studies on larger population in this environment are however indicated.

Primary hyperparathyroidism in Saudi Arabia: a review of 46 cases.

Records of 46 patients who were treated for primary hyperparathyroidism at King Khalid University Hospital, Riyadh Saudi Arabia from 1st July 2000 to 30th June 2006 were reviewed. Mean age at diagnosis was 44 years (range 13-70 years) and average duration of symptoms was 39 months (1 month to 11 years). There were 35 females and 11 males with a ratio of 3.2:1. Bone pains were the major symptoms at presentation in 45.7% followed by no symptom in 23.9%, renal stones in 15.2%, polyuria in 6.5%, while 4.3% each presented with depression, and constipation. Males had significantly more severe disease with higher serum calcium, higher urinary calcium excretion, and higher serum creatinine. Ninety six percent of patients had successful surgery and 4% (two patients) each had recurrence and hungry bone syndrome. It is concluded that PHPT in Saudi Arabia continues to be a symptomatic disorder with skeletal and renal manifestations occurring at a younger age and males having more severe disease. Further prospective studies are needed to verify our findings.

Hepatitis B and C virus and hepatocellular carcinoma.

Antibody to hepatitis C virus (anti-HCV) was detected in 18.7% of patients with hepatocellular carcinoma (HCC) and in 10.9% of controls (P < 0.001). The corresponding prevalences of hepatitis B surface antigen (HBsAg) were 59.3% and 50.0% (P < 0.001). Using patients with non-hepatic disease as controls, stepwise logistic regression analysis indicated that both anti-HCV (odds ratio 6.88%; 95% confidence interval [CI] 1.63-9.77) and HBsAg (odds ratio 6.46; 95% CI 1.68-18.13) were independent risk factors for HCC. Calculation of the incremental odds ratio indicated no interaction between hepatitis B virus (HBV) and HCV. Blood transfusion was a significant risk factor for acquiring HCV infection with odds ratios of 5.48 (95% CI 1.07-29.0) and 2.86 (95% CI 1.31-22.72) for HCC cases and controls, respectively. The mean age of HCC cases with HBsAg and anti-HCV was lower than that of HCC patients with anti-HCV alone (P < 0.01). It is concluded that there is a high rate of HBV infection, and a low rate of HCV infection, among Nigerian patients with HCC. However, HBV and HCV are independent risk factors for the development of HCC, with HBV having an effect more rapidly. Screening of blood products for transfusion might minimize the risk of HCV transmission.

Cutaneous manifestations of liver cirrhosis in an African (negroid) population.

Sixty negroid patients with liver cirrhosis were examined for their cutaneous features at the University College Hospital, Ibadan, Nigeria. When compared with age and sex matched controls, the cirrhotic patients had significantly lower body temperature, onycholysis and hyperpigmented palmo-plantar macular areas (p < 0.05). Until now, these features have not been previously associated with liver cirrhosis. Other cutaneous signs such as sparse silky hair, female public hair pattern, digital clubbing, leuconychia, ankle oedema and corneal jaundice are found more commonly in cirrhotic patients (p < 0.05) and have been previously documented. All these features in a middle-aged man with hepatomegaly may be of added distinctive value particularly in many rural centres in tropical countries where facilities for definitive histological diagnosis are frequently lacking. The relevance of some of these cutaneous features in the light of the pattern described in Caucasians is also discussed.

Increased neuropeptide Y concentrations in specific hypothalamic regions of lactating rats: possible relationship to hyperphagia and adaptive changes in energy balance.

Lactation is accompanied by hyperphagia and a reduction in brown adipose tissue (BAT) thermogenesis, which are unexplained. Neuropeptide Y (NPY) powerfully stimulates feeding and inhibits BAT thermogenesis when injected into the paraventricular nucleus and other specific regions of the rat hypothalamus. We have tested the hypothesis that hypothalamic NPY activity is increased in lactating rats. Lactating rats consumed over four times as much food as nonlactating controls (n = 10; p < 0.001). Final plasma insulin concentrations in lactating rats were lower than in controls (6.8 +/- 0.8 vs. 11.7 +/- 2.1 pmol/l; p < 0.05) although plasma glucose and corticosterone concentrations were comparable (p > 0.05). Lactating rats showed significantly higher NPY levels than controls in specific hypothalamic regions, namely the arcuate nucleus-median eminence complex (a 41% rise; p < 0.001), paraventricular nucleus (35%; p < 0.001), ventromedial nucleus (66%; p = 0.003), and dorsomedial nucleus (78%; p < 0.001). Other hypothalamic regions showed no significant differences between groups. Increased NPY concentrations in specific hypothalamic regions, particularly the arcuate nucleus where NPY is synthesized, suggest increased activity of the hypothalamic NPYergic system in lactation. Neuropeptide Y may mediate hyperphagia and reduced BAT thermogenesis in lactation. Hypoinsulinemia may be a stimulus to hypothalamic NPY in lactation, as has been postulated in other conditions of negative energy balance.

Effects of chronic vanadate administration in the STZ-induced diabetic rat. The antihyperglycemic action of vanadate is attributable entirely to its suppression of feeding.

Vanadate treatment can lower glycemia in diabetic rats. This action is generally attributed to vanadate's insulinomimetic properties, but vanadate also inhibits feeding, which could lower blood glucose. We therefore assessed the contribution of hypophagia to vanadate's antihyperglycemic action in a 3-week study of streptozocin-induced (STZ) diabetic rats. Untreated diabetic rats (n = 8) ate 54% more food than nondiabetic control rats (P < 0.001). Diabetic rats given sodium metavanadate (0.5 mg in 0.5 ml of water by gavage twice daily; n = 8) had significantly lower food intakes (P < 0.001) than untreated diabetic rats. In vanadate-treated diabetic rats, blood glucose levels were significantly lower than in untreated diabetic rats (P < 0.001). Untreated diabetic rats pair-fed to the food intake of the vanadate-treated diabetic rats (n = 8) showed virtually identical blood glucose falls (P > 0.05 vs. vanadate-treated diabetic rats). Vanadate treatment did not affect plasma insulin concentrations in diabetic rats. In nondiabetic rats (n = 8), vanadate treatment significantly reduced food intake (P < 0.05) and also lowered plasma insulin concentrations (P < 0.05) without significantly affecting glycemia. To investigate the mechanism of vanadate's hypophagic effect, we also measured regional hypothalamic levels of neuropeptide Y (NPY), a potent central appetite stimulant that is thought to drive hyperphagia in STZ-induced diabetes. Hypothalamic NPY concentrations rise markedly in diabetes and are normalized by insulin replacement. Unlike insulin, vanadate treatment did not normalize regional hypothalamic NPY concentrations in diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased neuropeptide Y concentrations in specific hypothalamic nuclei of the rat following treatment with methysergide: evidence that NPY may mediate serotonin's effects on food intake.

Neuropeptide Y (NPY) is a potent central appetite stimulant found in hypothalamic neurons that have close anatomical associations with neurons containing serotonin, a powerful anorectic agent. To determine whether the two neurotransmitters interact functionally, we have studied the effects on regional hypothalamic NPY concentrations of acute and chronic administration of methysergide, a 5-HT1BC/serotonin receptor antagonist. Chronic methysergide treatment (10 mg/kg/day) was given by subcutaneously implanted osmotic minipumps (n = 8). Acute effects of methysergide were determined 4 h after a single injection (10 mg/kg) in a separate group (n = 8). Controls (n = 8) had implanted minipumps delivering saline, and also received a saline injection 4 h before sacrifice. Food intake was significantly increased (p < 0.01) by both acute and chronic methysergide treatment. In the chronically treated rats, NPY levels were significantly increased over controls in the arcuate nucleus (ARC; by 41%, p = 0.02) and paraventricular nucleus (PVN; by 40%, p < 0.01). Acute methysergide treatment also increased NPY concentrations in the ARC (by 81%, p < 0.01) and PVN (by 30%, p < 0.01). Methysergide administration, which stimulated feeding, therefore raised NPY concentrations in the ARC, where NPY is synthesized, and in the PVN, a major site of NPY release where NPY injection induces hyperphagia. These findings suggest that NPYergic and serotoninergic innervations in the hypothalamus interact to regulate food intake, and raise the possibility that increased NPY release may mediate the hyperphagic effect of serotoninergic 5-HT1BC/receptor blockade.

Acute hyperinsulinemia increases neuropeptide Y concentrations in the hypothalamic arcuate nucleus of fasted rats.

Neuropeptide Y, a major hypothalamic peptide, stimulates feeding, insulin secretion and weight gain when injected intrahypothalamically. Hypothalamic NPY may be regulated by insulin availability at hypothalamic level, as its activity is apparently inhibited by intrahypothalamic insulin administration and is stimulated under insulin-deficient conditions. To determine the effects of acute physiological hyperinsulinemia, we measured regional hypothalamic NPY levels in rats during a hyperinsulinemic, euglycemic clamp. Seven male Wistar rats with implanted jugular cannulae, fasted for 24 h, were infused with insulin at 100 mU/h together with variable-rate glucose to maintain euglycemia (3.9 +/- 0.1 mmol/l), for 150 min. Controls were infused for the same period with polygeline vehicle alone (n = 8), and had blood glucose concentrations of 4.0 +/- 0.5 mmol/l. Insulin levels were 80.2 +/- 3.9 mU/l in insulin-infused rats and 15.2 +/- 1.4 mU/l in polygeline-treated controls (p < 0.001). NPY levels, measured by radioimmunoassay, were significantly higher in the arcuate nucleus/median eminence (ARC/ME) of hyperinsulinemic rats than in controls (4.8 +/- 1.2 vs 2.5 +/- 0.6 fmol/micrograms protein; p < 0.001), but were comparable with controls in 7 other hypothalamic regions. Acute physiological hyperinsulinemia therefore increases NPY levels selectively in the ARC/ME. Insulin could cause NPY accumulation in the ARC by blocking its transport to NPY-sensitive areas. This would be consistent with the suggestions that insulin inhibits hypothalamic NPY activity and also acts as a central satiety factor.

Peripheral insulin administration attenuates the increase in neuropeptide Y concentrations in the hypothalamic arcuate nucleus of fasted rats.

Fasting increases neuropeptide Y (NPY) concentrations in the arcuate nucleus (ARC), its site of synthesis, and in other regions of the rat hypothalamus. Neuropeptide Y is a potent central orexigenic agent and may therefore stimulate appetite during fasting. We tested the hypothesis that low plasma insulin levels stimulate ARC levels of NPY in fasted rats. Compared with freely fed controls (n = 8), rats fasted for 72 h (n = 8) showed significantly lower plasma insulin levels (28.9 +/- 1.6 vs. 52.6 +/- 5.7 pmol/l; p < 0.001) and higher ARC NPY concentrations (14.2 +/- 1.8 vs. 8.4 +/- 2.2 fmol/micrograms protein; p < 0.001). Fasted rats treated with subcutaneous insulin (5 U/kg/day; n = 10), which nearly normalized plasma insulin (46.6 +/- 2.8 pmol/l), showed intermediate ARC NPY levels (11.2 +/- 1.4 fmol/micrograms protein; p < 0.01 vs. controls and untreated fasted rats). Insulin administered peripherally, therefore, attenuates fasting-induced NPY increases in the ARC, supporting the hypothesis that hypoinsulinemia stimulates hypothalamic NPY.