Temporal trends in the clinical presentation of Graves' orbitopathy: a single-center retrospective study.

PURPOSE: Graves' ophthalmopathy (GO) is an autoimmune disease that affects orbital soft tissues and represents the most common extrathyroidal manifestation of Graves' disease (GD). The European Group of Graves' Ophthalmopathy (EUGOGO) has attempted to shed light on the European epidemiological picture of GO, suggesting that GO in newly diagnosed patients in recent years has a trend towards a less severe clinical presentation. There are no studies that focus this issue on the population of our area; we aimed to evaluate the trend of GO clinical presentation in our outpatient clinic through an observation period of 10 years. METHODS: We compared 55 consecutive patients, 11 males (F) and 44 females (M), who came to our observation from January 2005 to December 2006 [Group 1 (G1)], with 56 patients, 15 males, and 41 females, who were referred to us from 2015 to 2016 [Group 2 (G2)]. We studied the following putative predictors of GO presentation and severity: thyroid function, smoking, diabetes, hypercholesterolemia, time from GO diagnosis to referral to our thyroid centre (TGOD), sex and age. RESULTS: GO severity was significantly reduced in G2 vs. G1 (p = 0.04). TGOD ≥ 3 months was related to clinical characteristics of GO (severity and Clinical Activity Score ≥ 4) and was an independent predictor of GO severity (p = 0.01). The other variables evaluated had no independent effects. CONCLUSIONS: We found that GO severity at presentation was significantly reduced over a ten-year observation period (2005-2006 vs. 2015-2016) in GO patients referred to our tertiary thyroid centre. TGOD ≥ 3 months was an independent predictor of GO severity.

Very low serum IGF-1 levels are associated with vertebral fractures in adult males with beta-thalassemia major.

PURPOSE: Patients with beta-thalassemia major (BTM) often develop several endocrine disorders due to chronic iron overload. They are also prone to osteoporosis and vertebral fractures. Plasmatic insulin-like growth factor-1 (IGF-1) levels are often low in subjects with BTM, which origin is multifactorial. The aim of this study was to evaluate a possible relationship between serum IGF-1 levels and the presence of osteoporosis and/or vertebral fractures. METHODS: We retrospectively evaluated the occurrence of vertebral fractures in 30 adult male patients affected by BTM (mean age 43.3 ± 7.9 years) with low serum IGF-1 (median value 52.4 ng/ml, 38.5-83.4). Only 6 of them (20.0%) were diagnosed with GH deficiency (GHD) after GHRH/arginine stimulation test, while 23 (76.7%) had osteoporosis and 12 (40.0%) had known vertebral fractures. All patients except one also showed at least one endocrine disorder. RESULTS: Serum IGF-1 was significantly lower in BTM patients with vertebral fractures compared to patients without vertebral fractures (U = 41.0, p = 0.005) while it was not significantly different between patients with low bone mass compared to patients without low bone mass. The diagnosis of GHD was significantly associated with lower serum IGF-1 (p = 0.001) and vertebral fractures (p = 0.002) but not with low bone mass. After ROC analysis, we found that very low IGF-1 (≤ 50.0 ng/dl) was associated with vertebral fractures (sensitivity 83.3%, specificity 75.0%) and was also predictive of GHD (sensitivity 75.0%, specificity 100.0%). CONCLUSION: Our study shows that, in male patients with BTM, serum IGF-1 ≤ 50.0 ng/dl is a marker of vertebral fractures and it is predictive of a diagnosis of GHD.

Relationship between betacoronaviruses and the endocrine system: a new key to understand the COVID-19 pandemic-A comprehensive review.

BACKGROUND: A new harmful respiratory disease, called COVID-19 emerged in China in December 2019 due to the infection of a novel coronavirus, called SARS-Coronavirus 2 (SARS-CoV-2), which belongs to the betacoronavirus genus, including SARS-CoV-1 and MERS-CoV. SARS-CoV-2 shares almost 80% of the genome with SARS-CoV-1 and 50% with MERS-CoV. Moreover, SARS-CoV-2 proteins share a high degree of homology (approximately 95%) with SARS-CoV-1 proteins. Hence, the mechanisms of SARS-Cov-1 and SARS-Cov-2 infection are similar and occur via binding to ACE2 protein, which is widely distributed in the human body, with a predominant expression in endocrine tissues including testis, thyroid, adrenal and pituitary. PURPOSE: On the basis of expression pattern of the ACE2 protein among different tissues, similarity between SARS-Cov-1 and SARS-Cov-2 and the pathophysiology of COVID-19 disease, we aimed at discussing, after almost one-year pandemic, about the relationships between COVID-19 infection and the endocrine system. First, we discussed the potential effect of hormones on the susceptibility to COVID-19 infection; second, we examined the evidences regarding the effect of COVID-19 on the endocrine system. When data were available, a comparative discussion between SARS and COVID-19 effects was also performed. METHODS: A comprehensive literature search within Pubmed was performed. This review has been conducted according to the PRISMA statements. RESULTS: Among 450, 100 articles were selected. Tissue and vascular damages have been shown on thyroid, adrenal, testis and pituitary glands, with multiple alterations of endocrine function. CONCLUSION: Hormones may affect patient susceptibility to COVID-19 infection but evidences regarding therapeutic implication of these findings are still missing. SARS and COVID-19 may affect endocrine glands and their dense vascularization, impairing endocrine system function. A possible damage of endocrine system in COVID-19 patients should be investigated in both COVID-19 acute phase and recovery to identify both early and late endocrine complications that may be important for patient's prognosis and well-being after COVID-19 infection.

Association of autoimmune thyroid diseases, chronic atrophic gastritis and gastric carcinoid: experience from a single institution.

PURPOSE: Autoimmune polyendocrine syndromes (APS) type III are characterized by the association of autoimmune thyroid disease (ATD) with other autoimmune diseases such as diabetes, alopecia, pernicious anemia, vitiligo and chronic atrophic gastritis. A strong association between ATD and atrophic gastritis (AG) has been demonstrated. Moreover 10 % of patients affected by AG have a predisposition to develop gastric carcinoid and adenocarcinoma as a result of chronic hypergastrinemia caused by achlorhydria and subsequent ELC cells neoplastic transformation. METHODS: The aim of the study is to evaluate, in a consecutive series of patients followed for ATD in our outpatients clinic, the prevalence of AG. In the period 2004-2014, 242 patients with ATD underwent a screening performing APCA, Vitamin B12, ferritin, iron, and hemoglobin and red cells count measurements with subsequent gastroscopy in case of APCA positivity. RESULTS: We found 57/242 (23.5 %) patients with APCA positivity. Of these patients 33/57 (57.8 %), 31 F and 2 M, were affected by Graves disease; 24/57 (42.1 %) 21 F and 3 M by Hashimoto thyroiditis; 10/57 (17.5 %) presented with anemia, 14/57 (24.5 %) with vitamin B12 deficiency, 9/57 (15.7 %) with iron deficiency. In 2/57 a gastric carcinoid was found. CONCLUSIONS: Our data confirm the high association rate of AG in ATD which frequently is not an isolated disease but configure the picture of APS type III and need to be followed accordingly. An early diagnosis may be useful for diagnosis of gastric carcinoids and to explain and treat a gastric related L-thyroxine malabsorption and presence of chronic unexplained anemia.

Type 2 diabetic patients with Graves' disease have more frequent and severe Graves' orbitopathy.

BACKGROUND AND AIMS: Due to the worldwide increasing prevalence of diabetes (DM), patients with both diabetes and Graves' disease (GD) have become more frequent. Sporadic reports indicate that Graves' orbitopathy (GO), a GD complication that affects orbital soft tissues, can be severe in DM patients. The relationship between these diseases is not well understood. This study aims at evaluating the association of GD and GO with autoimmune and non-autoimmune diabetes (DM) and to assess diabetic features that influence GD and GO prevalence and severity. METHODS AND RESULTS: This retrospective study evaluated GD, GO and DM association in 1211 consecutive GD patients (447 with GO and 77 with DM). A case-control study was carried out to evaluate DM relationship with GO severity by comparing at 1:2 ratio GO patients with or without DM. A strong association was found between GD and T1DM (p = 0.01) but not T2DM. Instead, the presence of GO was strongly associated with T2DM (p = 0.01). Moreover, GO was more frequently severe in GD patients with T2DM (11/30 or 36.6%) than in those without T2DM (1/60 or 1.7%, p = 0.05). T2DM was the strongest risk factor for severe GO (OR = 34.1 vs. 4.4 p < 0.049 in cigarette smokers). DM duration, obesity and vascular complications, but not metabolic control were significant determinants of GO severity. CONCLUSIONS: GD is associated with T1DM but not with T2DM, probably because of the common autoimmune background. GO, in contrast, is more frequent and severe in T2DM, significantly associated with obesity, diabetes duration and diabetic vasculopathy but not metabolic control.

The tall cell variant of papillary thyroid carcinoma: clinical and pathological features and outcomes.

BACKGROUND: The tall cell variant (TCV) is a relatively rare variant of papillary thyroid cancer. Since a controversy exists whether or not the TCV has a worse outcome, the aim of our study was to retrospectively compare the clinicopathological features and outcomes in a group of TCV patients and a larger group of patients with classical papillary thyroid carcinoma (cPTC). SUBJECTS AND METHODS: Data from 30 TCV and 293 cPTC patients were analyzed. Among the 293 cPTC, we also selected a "high-risk" cPTC group (no.=103) that was treated with the same protocol used for the TCV patients. All data were managed by Cox analysis. RESULTS: Compared to all cPTC patients, TCV subjects displayed only a significantly higher rate of extrathyroid extension. At multivariate analysis, TCV was not an independent variable for the prediction of a high risk of persistent/recurrent disease. At the last follow-up observation, there was no difference in the disease status between the TCV and all cPTC patients. Moreover, "high-risk" cPTC patients had a significant increase in persistent/recurrent disease. CONCLUSIONS: In our study, although the TCV histotype is associated with a higher prevalence of extrathyroid extension, it is characterized by an outcome that is not significantly different from that of all cPTC patients and is more favorable than that of "high-risk" cPTC patients. Only those TCV patients classified as "high risk" based on specific pathological and clinical features, according to current guidelines, should be treated aggressively, such as with a total thyroidectomy, neck lymph node dissection or ablative radioiodine treatment.

A novel methodology for epidemic risk assessment of COVID-19 outbreak.

We propose a novel data-driven framework for assessing the a-priori epidemic risk of a geographical area and for identifying high-risk areas within a country. Our risk index is evaluated as a function of three different components: the hazard of the disease, the exposure of the area and the vulnerability of its inhabitants. As an application, we discuss the case of COVID-19 outbreak in Italy. We characterize each of the twenty Italian regions by using available historical data on air pollution, human mobility, winter temperature, housing concentration, health care density, population size and age. We find that the epidemic risk is higher in some of the Northern regions with respect to Central and Southern Italy. The corresponding risk index shows correlations with the available official data on the number of infected individuals, patients in intensive care and deceased patients, and can help explaining why regions such as Lombardia, Emilia-Romagna, Piemonte and Veneto have suffered much more than the rest of the country. Although the COVID-19 outbreak started in both North (Lombardia) and Central Italy (Lazio) almost at the same time, when the first cases were officially certified at the beginning of 2020, the disease has spread faster and with heavier consequences in regions with higher epidemic risk. Our framework can be extended and tested on other epidemic data, such as those on seasonal flu, and applied to other countries. We also present a policy model connected with our methodology, which might help policy-makers to take informed decisions.

Insulin analogues differently activate insulin receptor isoforms and post-receptor signalling.

AIMS/HYPOTHESIS: Five insulin analogues, with modified insulin-like molecular structures, are currently approved for treating diabetic patients. They activate cell signalling and biological responses via insulin receptor isoforms (IR-A and IR-B), each having specific characteristics for eliciting cell responses. The molecular and biological effects of these analogues on receptor isoforms in comparison to native insulin are not well defined, and their effects on the IGF1 receptor (IGF1R) are controversial. The characterisation of these effects was the aim of the present study. METHODS: Short-acting (insulin lispro [B28Lys,B29Pro human insulin], insulin aspart [B28Asp human insulin], insulin glulisine [B3Lys,B29Glu human insulin]) and long-acting (insulin glargine [A21Gly,B31Arg,B32Arg human insulin], insulin detemir [B29Lys(epsilon-tetradecanoyl),desB30 human insulin]) insulin analogues were studied in three engineered cell models (R(-), IGF1R-deprived mouse fibroblasts transfected with either only human IR-A or IR-B or IGF1R). Receptor binding and phosphorylation, AKT and extracellular signal-regulated kinase (ERK) activation, cell proliferation and colony formation were evaluated after exposing the cells to each analogue and were compared with insulin, IGF1 and the carcinogenic analogue B10Asp. RESULTS: All short-acting insulin analogues produced molecular and biological effects similar but not identical to those of insulin. Relative to insulin, long-acting analogues more strongly activated the ERK pathway via both IR-A and IGF1R as well as increased cell proliferation. At the concentration tested, no analogue (except B10Asp via IR-A) had increased transforming activity. CONCLUSIONS/INTERPRETATION: Cell models that permit comparisons of the activity of insulin to that of insulin analogues via each receptor individually indicate that only minor differences exist between insulin and short-acting analogues. By contrast, long-acting analogues activate the mitogenic signalling pathway more effectively than insulin and cause increased cell proliferation.

Effect of octreotide on growth hormone, IGF-I, IGFBP-3, glucagon, cortisol and epinephrine response to insulin-induced hypoglycaemia in insulin-dependent diabetic patients.

The purpose of the study was to investigate the effects of octreotide on the response of counterregulatory hormones to insulin-induced hypoglycaemia in 9 Type 1 diabetic patients without autonomic neuropathy. During an euglycaemic clamp, saline or octreotide (50 mcg) was randomly injected subcutaneously. Patients were then clamped to hypoglycaemic levels (2.5 mmol/l), and hormonal response was evaluated after 30 min of hypoglycaemia. Although octreotide suppressed both GH (0.5 +/- 0.01 vs 9.5 +/- 0.9 ng/ml, p < 0.001) and glucagon (110 +/- 9 vs 165 +/- 10 pg/ml, p < 0.05) responses, it did not affect cortisol, epinephrine, IGF-1 and IGFBP-3 levels. The time required for recovery from hypoglycaemia was longer after octreotide (19.1 +/- 1.2 min vs 14.3 +/- 0.9 min, p < 0.05), and a greater amount of infused glucose was needed to reach normoglycaemia (g 24.6 +/- 1.2 vs 17.7 +/- 1.3, p < 0.05). These findings suggest that administration of octreotide to insulin-treated Type 1 diabetic patients may impair anti-hypoglycaemic counterregulatory mechanisms through suppression of glucagon and GH responses.

Effects of octreotide on glycaemic control, glucose disposal, hepatic glucose production and counterregulatory hormones secretion in type 1 and type 2 insulin treated diabetic patients.

We studied the effects of continuous subcutaneous infusion of octreotide (100 micrograms/day for 5 days) on glycaemic values, counterregulatory hormones secretion, hepatic glucose production (HGP) and glucose disposal during an euglycaemic clamp in 7 C-peptide-negative type 1 diabetic patients and 7 C-peptide positive insulin-treated type 2 diabetic patients. In type 1, but not type 2 diabetic patients, octreotide significantly reduced glycaemic values (P < 0.005) and also diminished HGP during an euglycaemic clamp (P < 0.05). However, insulin stimulated global glucose uptake remained unchanged. GH, glucagon, IGF-I, IGFBP-3 levels, were significantly lowered by octreotide in both type 1 and type 2 diabetic patients whereas cortisol and epinephrine remained unmodified. Moreover in type 2 diabetic patients both basal (P < 0.05) and after-meal (P < 0.01) C-peptide secretion was reduced by octreotide. These data point to different metabolic effects of octreotide in type 1 versus type 2 diabetic patients with the drug only being able to reduce glycaemic values and HGP in the former but not in the latter subjects. The failure of octreotide to diminish glycaemic values and HGP in type 2 diabetic patients in spite of its ability to lower GH and glucagon may probably depend on temporary blockage of residual endogenous insulin secretion induced by octreotide administration.

A simplified diagnostic test for ambulatory screening of peripheral diabetic neuropathy.

The reliability and reproducibility of Michigan Neuropathy Screening Instrument (MNSI), a recently proposed simple test for ambulatory screening of peripheral diabetic neuropathy (PDN), was evaluated on 80 diabetic patients. MNSI was carried out by two diabetologists and repeated after a week. It consisted of the sum of scores varying from 0 to 1 for each abnormality revealed in foot appearance, achilles reflexes presence and vibratory threshold (VPT) by tuning fork (maximum score = 8). Then patients had to go to neurologist for PDN diagnosis by a quantitative neurological examination and electrophysiological evaluation, the so named Michigan Diabetic Neuropathy Score (MDNS) and the results compared with MNSI score according to one of the two observers. The inter-observer reproducibility of MNSI was 88.75% the within observer reproducibility was 95 and 94%, respectively, for each observer with good correlation between the two measurements (P < 0.001). The MNSI score of 2.5 as a cut-off appeared to be reliable for ambulatory screening of suspected PDN (false positive and false negative = 2.5%; specificity and sensitivity = 75% and 78.6%, respectively). In conclusion MNSI by using 2.5 score as cut-off may be considered a rapid, simple, reproducible and reliable test for rapid ambulatory screening of PDN from the diabetologists.

Effect of octreotide on insulin requirement, hepatic glucose production, growth hormone, glucagon and c-peptide levels in type 2 diabetic patients with chronic renal failure or normal renal function.

Aim of this study was to investigate whether octreotide, a synthetic somatostatin analogue that inhibits growth hormone, insulin and glucagon secretion and improves glycaemic control in insulin dependent diabetic patients was able to exert similar effects in insulin treated type 2 diabetic patients with chronic renal failure who have high plasma glucagon levels. For this purpose saline or octreotide was randomly administered by continuous subcutaneous infusion (100 mcg/daily) in addition to usual insulin treatment for 5 days to six type 2 insulin treated diabetic patients with chronic renal failure and to six type 2 patients with normal renal function, as a control group. At day 3 of insulin plus saline or insulin plus octreotide treatment, total glucose uptake and hepatic glucose production (HGP) were investigated during an euglycemic clamp; at day 5 GH, glucagon and C-peptide plasma levels were evaluated. Octreotide treatment lowered endogenous insulin secretion (evaluated by C-Peptide levels assay), GH and glucagon in all patients, but caused a significant reduction of daily insulin requirement (32 +/- 14 I.U. vs 41 +/- 19 I.U., P<0.02) only in patients with renal failure. HGP was significantly (P<0.05) lowered in patients with renal failure but glucose uptake remained unchanged. The lowering effect of octreotide on insulin requirement in diabetic patients with renal failure in spite of the contemporaneous inhibition on insulin secretion could be explained on the basis of the greater reduction of glucagon levels which are very elevated in these patients as compared to patients with normal renal function. The lowering of glucagon could decrease HGP and, consequently, insulin requirement.

Diabetic neuropathy: prevalence, concordance between clinical and electrophysiological testing and impact of risk factors.

UNLABELLED: The aim of this study was to assess the prevalence of various forms of diabetic neuropathy (DN), by clinical and electrophysiological tests, on 374 diabetic patients (66 with type 1 and 308 with type 2 diabetes mellitus) and the concordance between clinical and electroneurological alterations and relative risk factors impact. The overall prevalence of DN, according to the Saint Antonio Conference criteria, was 44.9% (28.88% somatic, 14.44% mixed and 1.60% autonomic) without statistical difference between type 2 and type 1 diabetes (46.43% and 37.88% respectively). In 32.24% of patients nerve conduction velocity (NCV) abnormalities were present together with clinical signs or symptoms of neuropathy, while 12.68% presented only signs and/or symptoms. In addition 9.36% of patients showed alterations of NCV in the absence of clinical signs or symptoms of neuropathy. The most frequent form was asymptomatic (30.21%), followed by symptomatic neuropathy (12.83%); rare was the severe neuropathy. Relative risk increased for diabetes duration > 20 years (p < 0.0001). IN CONCLUSION: 1) the Saint Antonio Consensus Conference criteria can be considered the most complete test for neuropathy diagnosis; 2) NCV alterations may not be concordant with signs-symptoms of neuropathy; 3) the duration of diabetes seems to be the most important risk factor.

[Effect of octreotide on blood glucose levels in poorly compensated insulin-dependent diabetics on insulin treatment]. / Effetti dell'octreotide sui livelli glicemici in diabetici insulino-dipendenti mal compensati con trattamento insulinico.

The metabolic effects of a long-acting somatostatin analogue, octreotide, in type I diabetic patients on conventional insulin therapy have been evaluated. Octreotide has been administered by subcutaneous continuous infusion employing a minipump; in 10 patients the infusion was performed from 08.00 a.m. to 08.00 p.m. and in 7 patients from 08.00 p.m. to 08.00 a.m. In both groups the drug dose was 50 mcg/12h and before starting the infusion an additional dose of 12.5 mg was rapidly injected s.c. In a third group of 8 patients octreotide was administered at a dosage of 50 mcg by subcutaneous injections at 07.00 a.m.; 3.00 p.m.; 11.00 p.m. A significant reduction of glucose levels was obtained in all patients and the results observed by minipump or by multiple injections were superimposable. It is to note that the daily drug dose employed by minipump was smaller. The evaluation of octreotide usefulness, in addition to conventional insulin therapy, in the management of type I diabetic patients, needs further extensive studies.

Evaluation of endocrine tests. A: the TRH test in patients with hyperprolactinaemia.

BACKGROUND: In a previous study, we determined reference values for basal and thyrotropin-releasing hormone (TRH)-stimulated plasma concentrations of prolactin (PRL). The aim of the present study was to determine the clinical usefulness of the PRL response to TRH in the work-up of patients with hyperprolactinaemia. METHODS: We studied 92 consecutive patients referred for evaluation of hyperprolactinaemia. Patients with confirmed hyperprolactinaemia were divided into three groups: group A (pharmacological hyperprolactinaemia; n=2), group B (pathological hyperprolactinaemia; n=6) and group C (all other patients). Patients in group C underwent MRI of the pituitary and were subdivided into C1 (normal pituitary on MRI; n=6), C2 (slightly abnormal MRI; n=21), and C3 (evident microadenoma or macroadenoma on MRI; n=25 and 12, respectively). The MRI was technically insufficient in four patients. Basal PRL as determined by fluoroimmunometric assay and the PRL response to 400 microg TRH were determined in all patients. RESULTS: Hyperprolactinaemia was confirmed in 83% of the referred patients. Non-response, defined as a <2.5-fold PRL increase after TRH, occurred in one patient (50%) in group A, in 66% of patients in group B and in 99% of patients in group C. Within group C, basal PRL was not different between group C1 and C2, but higher (p=0.06) in group C3. The absolute PRL increase after TRH did not differ between the three subgroups. The relative PRL increase was smaller (p=0.03) in group C3 but overlapped considerably with groups C1 and C2. All patients except one in group C were so-called non-responders. Basal PRL and absolute PRL increases after TRH correlated with the adenoma diameter on MRI (r=0.66, p=0.0002 and r=0.49, p=0.008, respectively). CONCLUSION: In patients referred for elevated serum PRL, hyperprolactinaemia should be confirmed under standardised conditions. The absolute or relative PRL increase after 400 microg TRH does not help to differentiate between patients with prolactinoma or idiopathic hyperprolactinaemia. Therefore, the TRH stimulation test is not useful in the work-up of hyperprolactinaemia.

Establishment of reference values for endocrine tests. II: Hyperprolactinemia.

BACKGROUND: In patients with hyperprolactinemia, the thyrotropin-releasing hormone (TRH) stimulation test is widely applied to distinguish prolactinoma from other causes of hyperprolactinemia. In the present study, we established reference values for the plasma concentration of prolactin (PRL) and its response to TRH. METHODS: Basal PRL and the PRL response to 400 micrograms TRH i.v. was determined in 50 subjects recruited from the general population, equally distributed according to sex and age between 20 and 69 years. PRL was determined by a fluoroimmunometric assay. Reference values are given as the observed range. RESULTS: Plasma concentrations of PRL were 4.0-25 micrograms/l (median: 10.0 micrograms/l) in women and 0.5-19.0 micrograms/l (median: 8.5 micrograms/l) in men (p = 0.11). The peak PRL concentration after stimulation with TRH was slightly higher in women (median: 51 micrograms/l) than in men (median: 41 micrograms/l; p = 0.04) and was reached at t = 20 min in all subjects. The relative increase in plasma PRL (median: 440%) did not show a statistically significant effect of age or sex. In 12 subjects (24%), the relative increase in plasma PRL was lower than 250%, which has traditionally been considered the minimum cutoff for a normal response. There were no effects of smoking and alcohol, but regular ingestion of liquorice was associated with lower basal (p = 0.03) and lower stimulated (p = 0.05) plasma concentrations of PRL. CONCLUSIONS: The present study provides reference values for basal and TRH-stimulated plasma concentrations of PRL.

Lack of pharmacological effect of subcutaneous octreotide in an insulin-dependent diabetic patient: reversal after mixing with aprotinin.

Octreotide, a synthetic analogue of somatostatin, may improve metabolic control and reduce GH and glucagon levels in insulin-dependent diabetic patients. We report hereto the case of an insulin-dependent diabetic patient in whom the subcutaneous continuous infusion of octreotide (150 micrograms/daily for six days) resulted ineffective on blood glucose levels, GH and glucagon. However, when octreotide was administered mixed together with aprotinin-an inhibitory of proteolytic enzymes (10,000 I.U. daily), it had lowering effect on blood glucose levels, GH and glucagon. We suggest the possibility that a local subcutaneous enzymatic degradation of octreotide may have occurred and that this degradation was blocked by aprotinin.

Different effects of octreotide by continuous night infusion at increasing rate or by evening injections at different times on morning hyperglycemia and growth hormone levels in insulin-dependent diabetic patients.

The effect of octreotide on morning hyperglycemia and GH levels was evaluated in eight insulin-dependent diabetic patients. Octreotide (50 mcg) was administered through subcutaneous injections at different hours (20:00, 22:00 and 24:00 h) or through continuous subcutaneous night infusion from midnight to 08:00 at increasing rate between 03:00 and 08:00 h. After octreotide injection at midnight we noticed a sharp decrease of both glycemia (p < 0.005) and GH (p < 0.05) at 04:00 h, but not at 08:00 h. Only the night continuous infusion at increasing rate was able to reduce glycemia and GH at 04:00 and at 08:00 h (p < 0.001 and p < 0.01 respectively). The injections of octreotide at 20:00 and 22:00 h lowered GH values at 24:00 h (p < 0.01 and p < 0.05 vs insulin alone) but did not show any significant effect on blood glucose levels and GH at 04:00 and 08:00 h. In conclusion, only the continuous subcutaneous night infusion of octreotide at increasing rate during the last hours of the night was able to reduce simultaneously morning hyperglycemia and GH levels in insulin-dependent diabetic patients, whereas evening subcutaneous injections at different times did not show any appreciable effect.

Determinants of longterm outcome of radioiodine therapy of sporadic non-toxic goitre.

OBJECTIVE: Radioiodine treatment is effective in reducing the size of sporadic nontoxic goitre, albeit at the expense of a high incidence of postradiation hypothyroidism. The decrease in goitre size, however, is not observed in all subjects, and little is known about recurrent goitre growth after 131I therapy. The aim of the present study was to evaluate which factors determine the longterm outcome of 131I treatment in patients with sporadic nontoxic nodular goitre, in terms of changes in both thyroid size and thyroid function. STUDY DESIGN: Retrospective follow-up study. PATIENTS: Fifty patients with sporadic nontoxic nodular goitre were evaluated who had been treated in our institution with 131I (mean dose 4.4 MBq/g thyroid) in the period 1988-95. Nine patients received a second dose of 131I and one a third. Median follow-up time was 41 months (range 24-115). MEASUREMENTS: Thyroid function was assesed by TSH and FT4 index, and thyroid volume by ultrasound in 46 patients, by scintiscan using the Himanka formula in three and by CT-scan in one. The response to treatment was defined as a decrease in thyroid volume of greater than 13% (i.e. the mean + 2SD of the coefficient of variation of volume measurements), and recurrent goitre as an increase in thyroid volume greater than 13% after an initial response. RESULTS: Goitre size decreased from a median value of 82 ml (range 17-325) to 37 ml (range 6-204) two years after 131I treatment, a median reduction of 49%. The decrease in goitre size was directly related to the dose of 131I (r = 0.50, P = 0.0003) and indirectly to baseline goitre size (r = - 0.35, P = 0.006). Seven patients (14%) were nonresponders, and four (8%) experienced recurrent goitre growth after 3-5 years. These 11 patients (22%) when compared to the remaining 39 responders (78%) had larger goitres with more often a dominant nodule, and had received a lower 131I dose. The efficacy of a second dose of 131I (median reduction in goitre size 37%) was comparable to the first dose. Hypothyroidism occurred in 24 patients (48%), mostly in the first two years after treatment; 11 had overt and 13 subclinical hypothyroidism. Kaplan Meier statistics indicated a probability of 58% for developing hypothyroidism after 8 years. Hypothyroid patients had a smaller initial goitre size and a higher prevalence of TPO antibodies and a family history of thyroid disease than the patients who remained euthyroid; the 131I dose did not differ between the two groups. CONCLUSIONS: The size of sporadic nontoxic goitres is reduced on average by 50% after a single dose of 4.77 MBq 131I/g thyroid. Independent determinants of the relative decrease in thyroid volume are administered 131I dose and initial goitre size. Nonresponders (14%) and those with late recurrence of goitre growth (8%) have larger goitres and more often dominant nodules than responders. Determinants of postradioiodine hypothyroidism (cumulative risk 58% after 8 years) are the presence of TPO antibodies, a family history of thyroid disease and a relatively small goitre. The implications of these findings are that the efficacy of a given 131I dose can be enhanced when administered at an earlier stage when the goitre is still smaller, albeit at the expense of an increased risk for developing hypothyroidism.