The modulation of platelet function by growth hormone in growth hormone deficient Hypopituitary patients.

BACKGROUND: Growth hormone deficiency (GHD) has been implicated in increased cardiovascular and cerebrovascular disease risk seen in hypopituitarism, however the mechanism remains speculative. We hypothesise that platelet abnormalities may play a contributory role. Herein we examined platelet behaviour in GHD hypopituitary patients, pre- and post-growth hormone (GH) replacement. METHODS: This study utilizes a physiological flow-based assay to quantify platelet function in whole blood from patient cohorts under arterial shear. Thirteen GH Naïve hypopituitary adults with GHD and thirteen healthy matched controls were studied. Patients were assessed before and after GH treatment. All other pituitary replacements were optimised before the study. In addition to a full endocrine profile, whole blood was labelled and perfused over immobilised von Willibrand factor (vWF). Seven parameters of dynamic platelet-vWF interactions were recorded using digital image microscopy and analysed by customised platelet tracking software. RESULTS: We found a significantly altered profile of platelet-vWF interactions in GHD individuals compared to healthy controls. Specifically, we observed a marked increase in platelets shown to form associations such as tethering, rolling and adherence to immobilized vWF, which were reduced post GH treatment. Speed and distance platelets travelled across vWF was similar between controls and pre-therapy GHD patients, however, this was considerably increased post treatment. This may indicate reduced platelet signaling resulting in less stable adhesion of platelets post GH treatment. CONCLUSIONS: Taken together observed differences in platelet behaviour may contribute to an increased risk of thrombosis in GHD which can in part be reversed by GH therapy.

Tissue Glucocorticoid Metabolism in Adrenal Insufficiency: A Prospective Study of Dual-release Hydrocortisone Therapy.

BACKGROUND: Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11ß-hydroxysteroid dehydrogenase (11ß-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy. The use of a once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may alter corticosteroid metabolism in vivo. STUDY DESIGN AND METHODS: Prospective crossover study assessing the impact of 12 weeks of DR-HC on systemic GC metabolism (urinary steroid metabolome profiling), cortisol activation in the liver (cortisone acetate challenge test), and subcutaneous adipose tissue (microdialysis, biopsy for gene expression analysis) in 51 patients with AI (primary and secondary) in comparison to IR-HC treatment and age- and BMI-matched controls. RESULTS: Patients with AI receiving IR-HC had a higher median 24-hour urinary excretion of cortisol compared with healthy controls (72.1 µg/24 hours [IQR 43.6-124.2] vs 51.9 µg/24 hours [35.5-72.3], P = .02), with lower global activity of 11ß-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11ß-HSD2 activity. Hepatic 11ß-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11ß-HSD1 in subcutaneous adipose tissue. CONCLUSION: Using comprehensive in vivo techniques, we have demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. This dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, which was ameliorated by treatment with DR-HC.

Treatment Guidelines for Hyponatremia: Stay the Course.

International guidelines designed to minimize the risk of complications that can occur when correcting severe hyponatremia have been widely accepted for a decade. On the basis of the results of a recent large retrospective study of patients hospitalized with hyponatremia, it has been suggested that hyponatremia guidelines have gone too far in limiting the rate of rise of the serum sodium concentration; the need for therapeutic caution and frequent monitoring of the serum sodium concentration has been questioned. These assertions are reminiscent of a controversy that began many years ago. After reviewing the history of that controversy, the evidence supporting the guidelines, and the validity of data challenging them, we conclude that current safeguards should not be abandoned. To do so would be akin to discarding your umbrella because you remained dry in a rainstorm. The authors of this review, who represent 20 medical centers in nine countries, have all contributed significantly to the literature on the subject. We urge clinicians to continue to treat severe hyponatremia cautiously and to wait for better evidence before adopting less stringent therapeutic limits.

Central diabetes insipidus from a patient's perspective: management, psychological co-morbidities, and renaming of the condition: results from an international web-based survey.

BACKGROUND: Central diabetes insipidus is a rare neuroendocrine condition. Data on treatment-associated side-effects, psychological comorbidities, and incorrect management are scarce. The aim of this study was to investigate patients' perspectives on their disease. METHODS: This study used a cross-sectional, web-based, anonymous survey, developed by endocrinologists and patient representatives, to collect the opinions of patients with central diabetes insipidus on management and complications of their disease, psychological comorbidities, degree of knowledge and awareness of the condition among health-care professionals, and renaming the disease to avoid confusion with diabetes mellitus (diabetes). FINDINGS: Between Aug 23, 2021, and Feb 7, 2022, 1034 patients with central diabetes insipidus participated in the survey. 91 (9%) participants were children and adolescents (37 [41%] girls and 54 [59%] boys; median age 10 years [IQR 6-15]) and 943 (91%) were adults (757 [80%] women and 186 [20%] men]; median age 44 years [34-54]). 488 (47%) participants had isolated posterior pituitary dysfunction and 546 (53%) had combined anterior and posterior pituitary dysfunction. Main aetiologies were idiopathic (315 [30%] of 1034 participants) and tumours and cysts (pre-surgical 217 [21%]; post-surgical 254 [25%]). 260 (26%; 95% CI [0·23-0·29]) of 994 patients on desmopressin therapy had hyponatraemia leading to hospitalisation. Patients who routinely omitted or delayed desmopressin to allow intermittent aquaresis had a significantly lower prevalence of hyponatraemia compared with those not aware of this approach (odds ratio 0·55 [95% CI 0·39-0·77]; p=0·0006). Of patients who had to be hospitalised for any medical reason, 71 (13%; 95% CI 0·10-0·16) of 535 patients did not receive desmopressin while in a fasting state (nil by mouth) without intravenous fluid replacement and reported symptoms of dehydration. 660 (64%; 0·61-0·67) participants reported lower quality of life, and 369 (36%; 0·33-0·39) had psychological changes subjectively associated with their central diabetes insipidus. 823 (80%; 0·77-0·82) participants encountered a situation where central diabetes insipidus was confused with diabetes mellitus (diabetes) by health-care professionals. 884 (85%; 0·83-0·88) participants supported renaming the disease; the most favoured alternative names were vasopressin deficiency and arginine vasopressin deficiency. INTERPRETATION: This is the largest survey of patients with central diabetes insipidus, reporting a high prevalence of treatment-associated side-effects, mismanagement during hospitalisation, psychological comorbidities, and a clear support for renaming the disease. Our data are the first to indicate the value of routinely omitting or delaying desmopressin. FUNDING: Swiss National Science Foundation, Swiss Academy of Medical Sciences, and G&J Bangerter-Rhyner-Foundation.

Management of cranial diabetes insipidus: clinical outcomes and patient perception of care.

Objective: There is growing recognition of morbidity and mortality that can occur in patients with cranial diabetes insipidus (CDI) during hospitalisation, due to prescribing errors and dysnatraemia, often related to confusion between CDI and diabetes mellitus among non-specialists. We aimed to investigate this. Methods: Data for each hospitalisation in patients with CDI attending Oxford University Hospital (OUH) were collected retrospectively. The same cohort were invited to complete a questionnaire by telephone. Results: One hundred and nine patients were included, median age was 42 (range: 6-80) years. Route of desmopressin was tablet, melt and nasal spray in 74%, 7% and 17% of patients, respectively, while two patients used a combination of tablet and nasal spray. There were 85 admissions to OUH by 38 patients between 2012 and 2021. Daily measurement of serum sodium was performed in 39% of admissions; hyponatraemia and hypernatraemia occurred in 44 and 15% of admissions, respectively. Endocrine consultation was sought in 63% of admissions post-2018. Forty-five of 78 patients (58%) self-reported ≥1 admission to any hospital since diagnosis. Of these, 53% felt their medical team did not have a good understanding of the management of CDI during hospital admission. Twenty-four per cent reported delay in administration of desmopressin, while 44% reported confusion between CDI and diabetes mellitus, often leading to unnecessary blood glucose monitoring. Conclusion: Dysnatraemia is common in hospitalised patients with CDI. More than half of patients perceived their medical team's understanding of CDI to be poor when admitted with intercurrent illness. A coordinated approach, including early consultation of specialists, frequent serum sodium monitoring, and education of hospital specialists is needed to address this.

The management of acute and chronic hyponatraemia.

Hyponatraemia is the most common electrolyte abnormality encountered in clinical practice; despite this, the work-up and management of hyponatraemia remain suboptimal and varies among different specialist groups. The majority of data comparing hyponatraemia treatments have been observational, up until recently. The past two years have seen the publication of several randomised control trials investigating hyponatraemia treatments, both for chronic and acute hyponatraemia. In this article, we aim to provide a background to the physiology, cause and impact of hyponatraemia and summarise the most recent data on treatments for acute and chronic hyponatraemia, highlighting their efficacy, tolerability and adverse effects.

Successful transition from insulin to sulfonylurea, on second attempt, in a 24-year-old female with neonatal diabetes secondary to KCNJ11 gene mutation.

Neonatal diabetes (NDM) is defined as diabetes that occurs in the first 6 months of life, the majority of cases are due to sporadic mutations. ATP-sensitive potassium channels located in the beta cells of the pancreas play a major role in insulin secretion and blood glucose homeostasis. Mutations that alter the function of these channels may lead to NDM. We report a case of a 26-year-old Irish woman who was diagnosed with NDM at the age of 4 weeks and treated as type 1 diabetes mellitus, with multiple daily injections of insulin with suboptimal glycaemic control and frequent episodes of hypoglycaemic. She underwent genetic testing for NDM and was diagnosed with a KCNJ11 gene mutation. She was transitioned to high dose glibenclamide at the age of 16 years, but the trial failed due to poor glycaemic control and patient preference, and she was restarted on insulin. At 24 years of age, she was successfully transitioned from insulin (total daily dose 50 units) to high dose sulfonylurea (SU) (glibenclamide 15 mg twice daily). This resulted in optimal control of blood glucose (HbA1C fell from 63 to 44 mmol/mol), lower rates of hypoglycaemic and better quality of life. This case demonstrates that a second trial of SU in later life may be successful.

Outcomes of endoscopic transsphenoidal surgery for Cushing's disease.

BACKGROUND: Transsphenoidal surgery (TSS) to resect an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma is the first-line treatment for Cushing's disease (CD), with increasing usage of endoscopic transsphenoidal (ETSS) technique. The aim of this study was to assess remission rates and postoperative complications following ETSS for CD. METHODS: A retrospective analysis of a prospective single-surgeon database of consecutive patients with CD who underwent ETSS between January 2012-February 2020. Post-operative remission was defined, according to Endocrine Society Guidelines, as a morning serum cortisol < 138 nmol/L within 7 days of surgery, with improvement in clinical features of hypercortisolism. A strict cut-off of < 50 nmol/L at day 3 post-op was also applied, to allow early identification of remission. RESULTS: A single surgeon (MJ) performed 43 ETSS in 39 patients. Pre-operative MRI localised an adenoma in 22 (56%) patients; 18 microadenoma and 4 macroadenoma (2 with cavernous sinus invasion). IPSS was carried out in 33 (85%) patients. The remission rates for initial surgery were 87% using standard criteria, 58% using the strict criteria (day 3 cortisol < 50 nmol/L). Three patients had an early repeat ETSS for persistent disease (day 3 cortisol 306-555 nmol/L). When the outcome of repeat early ETSS was included, the remission rate was 92% (36/39) overall. Remission rate was 94% (33/35) when patients with macroadenomas were excluded. There were no cases of CSF leakage, meningitis, vascular injury or visual deterioration. Transient and permanent diabetes insipidus occurred in 33 and 23% following first ETSS, respectively. There was one case of recurrence of CD during the follow-up period of 24 (4-79) months. CONCLUSION: Endoscopic transsphenoidal surgery produces satisfactory remission rates for the primary treatment of CD, with higher remission rates for microadenomas. A longer follow-up period is required to assess recurrence rates. Patients should be counselled regarding risk of postoperative diabetes insipidus.

Cardiometabolic and psychological effects of dual-release hydrocortisone: a cross-over study.

BACKGROUND: Adrenal insufficiency (AI) is associated with increased cardiovascular morbidity and mortality and reduced quality of life (QoL). Optimum glucocorticoid (GC) dosing and timing are crucial in the treatment of AI, yet the natural circadian secretion of cortisol is difficult to mimic. The once-daily dual-release hydrocortisone (DR-HC) preparation (Plenadren®), offers a more physiological cortisol profile and may address unmet needs. METHODS: An investigator-initiated, prospective, cross-over study in patients with AI. Following baseline assessment of cardiometabolic risk factors and QoL, patients switched from their usual hydrocortisone regimen to a once-daily dose equivalent of DR-HC and were reassessed after 12 weeks of treatment. RESULTS: Fifty-one patients (21 PAI/30 SAI) completed the study. Mean age was 41.6 years (s.d. 13), and 58% (n = 30) were male. The median daily HC dose before study entry was 20 mg (IQR 15-20 mg). After 3 months on DR-HC, the mean SBP decreased by 5.7 mmHg, P = 0.0019 and DBP decreased by 4.5 mmHg, P = 0.0011. There was also a significant reduction in mean body weight (-1.23 kg, P = 0.006) and BMI (-0.3 kg/m2, P = 0.003). In a sub-analysis, there was a greater reduction in SBP observed in patients with SAI when compared to PAI post-DR-HC. Patients reported significant improvements in QoL using three validated QoL questionnaires, with a greater improvement in PAI. CONCLUSION: Dual-release hydrocortisone decreases BP, weight and BMI compared with conventional HC treatment, even at physiological GC replacement doses. Additionally, DR-HC confers significant improvements in QoL compared to immediate-release HC, particularly in patients with PAI, which is also reflected in the patient preference for DR-HC.

Active management of hyponatraemia and mortality in older hospitalised patients compared with younger patients: results of a prospective cohort study.

INTRODUCTION: Hyponatraemia is associated with increased morbidity and mortality; the aetiology and outcomes of hyponatraemia in older patients have not been defined in prospective studies. METHODS: A single-centre 9-month prospective observational study in which clinical outcomes in hospitalised patients ≥ 65 years (older patients with hyponatraemia (OP-HN)) and those <65 years (young patients with hyponatraemia (YP-HN)) with hyponatraemia were analysed, and compared with eunatraemic controls (older patients with normonatraemia (OP-NN) and young patients with normonatraemia (YP-NN)). RESULTS: In total, 1,321 episodes of hyponatraemia in 1,086 patients were included; 437 YP-HN, median age 54 years (IQR 44,60) and 884 OP-HN, median age 77 years (IQR 71,82). A total of 1,120 consecutive eunatraemic control patients were simultaneously recruited; 690 OP-NN, median age 77 years (IQR 71,83) and 430 YP-NN, median age 52 years (IQR 41,58). Euvolaemic hyponatraemia was the commonest cause of hyponatraemia in both age groups (48% in YP-HN and 46% in OP-HN). Sixty-two percent of OP-HN received hyponatraemia-directed treatment within the initial 48 h, compared with 55% of YP-HN, P = 0.01. Despite the greater treatment rates in OP-HN, younger patients were 24% more likely to be discharged with normal plasma sodium concentration (pNa) compared with older patients, relative risk (RR) 1.24 (95% confidence interval (CI) 1.12-1.37), P < 0.001.Using OP-NN as the reference group, the RR of in-hospital death in OP-HN was 2.15 (95% CI 1.3-3.56), P = 0.002. Using YP-NN as the reference group, the RR of in-hospital death in YP-HN was 4.34 (95% CI 1.98-9.56), P < 0.001. CONCLUSION: Despite greater rates of HN-targeted treatment, the risk of in-hospital death is increased in older hyponatraemic patients compared with older eunatraemic controls. The impact of hyponatraemia on mortality is even greater in younger patients.

Active management of severe hyponatraemia is associated with improved mortality.

OBJECTIVE: Severe hyponatraemia (plasma sodium concentration, pNa <120 mmol/L) is reported to be associated with mortality rates as high as 50%. Although there are several international guidelines for the management of severe hyponatraemia, there are few data on the impact of treatment. DESIGN AND METHODS: We have longitudinally reviewed rates of specialist input, active management of hyponatraemia, treatment outcomes and mortality rates in patients with severe hyponatraemia (pNa <120 mmol/L) in 2005, 2010 and 2015, and compared the recent mortality rate with that of patients with pNa 120-125 mmol/L. RESULTS: Between 2005 and 2010 there was a doubling in the rate of specialist referral (32 to 68%, P = 0.003) and an increase in the use of active management of hyponatraemia in patients with pNa <120 mmol/L (63 to 88%, P = 0.02), associated with a reduction in mortality from 51 to 15% (P < 0.001). The improved rates of intervention were maintained between 2010 and 2015, but there was no further reduction in mortality. When data from all three reviews were pooled, specialist consultation in patients with pNa <120 mmol/L was associated with a 91% reduction in mortality risk, RR 0.09 (95% CI: 0.03-0.26), P < 0.001. Log-rank testing on in-hospital survival in 2015 found no significant difference between patients with pNa <120 mmol/L and pNa 120-125 mmol/L (P = 0.56). CONCLUSION: Dedicated specialist input and active management of severe hyponatraemia are associated with a reduction in mortality, to rates comparable with moderate hyponatraemia.

The effects of acute hyponatraemia on bone turnover in patients with subarachnoid haemorrhage: A preliminary report.

CONTEXT: Animal data and cross-sectional human studies have established that chronic hyponatraemia predisposes to osteoporosis; the effects of acute hyponatraemia on bone turnover have not been determined. Our objective was to test the hypothesis that acute hyponatraemia leads to dynamic effects on bone turnover. DESIGN: A prospective observational pilot study. METHODS: Bone turnover markers [C-terminal crosslinking telopeptide of type 1 collagen (CTX-1), N-propeptide of type 1 collagen (P1NP) and osteocalcin] were measured prospectively over one week in 22 eunatraemic patients with subarachnoid haemorrhage. Patients treated with glucocorticoids were excluded. RESULTS: Eight patients developed acute hyponatraemia, median nadir plasma sodium concentration 131 mmol/L (IQR 128-132), and 14 remained eunatraemic, nadir plasma sodium concentration 136 mmol/L (IQR 133-137). Significant main effects of hyponatraemia were found for P1NP (p = .02) and P1NP:CTX-1 ratio (p = .02), both fell in patients with acute hyponatraemia, with significant interaction between hyponatraemia and time from baseline for P1NP (p = .02). Significant main effects of time from baseline (p < .001) but not hyponatraemia (p = .07) were found for osteocalcin. For CTX-1, significant main effects of time from baseline (p = .001) but not hyponatraemia (p = .65) were found. There was a positive correlation between change in P1NP:CTX-1 ratio and nadir plasma sodium concentration, r = +.43, p = .04. Median serum cortisol (measured on days 1, 3 and 7) was higher in the hyponatraemia group than in those who remained eunatraemic, 545 nmol/L (IQR 373-778) versus 444 nmol/L (IQR 379-542) p = .03. CONCLUSION: These data suggest that acute mild hyponatraemia is associated with a reduction in bone formation activity.

The diagnostic utility of late night salivary cortisol (LNSF) and cortisone (LNSE) in Cushing's syndrome.

BACKGROUND: Measurement of late night salivary cortisol (LNSF) is useful in the identification of cyclical Cushing's syndrome (CS); the usefulness of its metabolite cortisone (late night salivary cortisone, LNSE) is less well described. AIM: The aim of this study was to determine the utility of measuring LNSE in patients with confirmed CS compared with other diagnostic tests and to analyse serial LNSF measurements for evidence of variable hormonogenesis. METHODS: This was a retrospective observational study including patients with confirmed CS in whom LNSF and LNSE were measured. RESULTS: Twenty-three patients with confirmed CS were included, 21 with Cushing's disease. LNSF had a sensitivity of 92%, LNSE 87% and combined LNSF/LNSE 94% per sample. Four patients had cyclical hormonogenesis, when the definition of one trough and two peaks was applied to LNSF measurements, and a fifth patient fell just outside the criteria. Six patients had evidence of variable hormonogenesis, defined as doubling of LNSF concentration on serial measurements. Sensitivity of 24-h urinary free cortisol (UFC) was 89% per collection. Sixteen patients had simultaneous measurements of LNSF and UFC; in three patients, they provided discordant results. CONCLUSION: LNSF appears more sensitive than LNSE and UFC in the diagnosis of CS, combining LNSF and LNSE results leads to superior sensitivity. Half of our cohort had evidence of cyclical or variable hormonogenesis. Fluctuations in LNSF did not always correlate with changes in UFC concentration, emphasising the importance of performing more than one screening test, particularly if pretest clinical suspicion is high.

Fluid Restriction Therapy for Chronic SIAD; Results of a Prospective Randomized Controlled Trial.

CONTEXT: Fluid restriction (FR) is the recommended first-line treatment for syndrome of inappropriate antidiuresis (SIAD), despite the lack of prospective data to support its efficacy. DESIGN: A prospective nonblinded randomized controlled trial of FR versus no treatment in chronic SIAD. INTERVENTIONS AND OUTCOME: A total of 46 patients with chronic asymptomatic SIAD were randomized to either FR (1 liter/day) or no specific hyponatremia treatment (NoTx) for 1 month. The primary endpoints were change in plasma sodium concentration (pNa) at days 4 and 30. RESULTS: Median baseline pNa was similar in the 2 groups [127 mmol/L (interquartile range [IQR] 126-129) FR and 128 mmol/L (IQR 126-129) NoTx, P = 0.36]. PNa rose by 3 mmol/L (IQR 2-4) after 3 days FR, compared with 1 mmol/L (IQR 0-3) NoTx, P = 0.005. There was minimal additional rise in pNa by day 30; median pNa increased from baseline by 4 mmol/L (IQR 2-6) in FR, compared with 1 mmol/L (IQR 0-1) NoTx, P = 0.04. After 3 days, 17% of FR had a rise in pNa of ≥5 mmol/L, compared with 4% NoTx, RR 4.0 (95% CI 0.66-25.69), P = 0.35. After 3 days, 61% of FR corrected pNa to ≥130 mmol/L, compared with 39% of NoTx, RR 1.56 (95% CI 0.87-2.94), P = 0.24. CONCLUSION: FR induces a modest early rise in pNa in patients with chronic SIAD, with minimal additional rise thereafter, and it is well-tolerated. More than one-third of patients fail to reach a pNa ≥130 mmol/L after 3 days of FR, emphasizing the clinical need for additional therapies for SIAD in some patients.

Management of central diabetes insipidus.

The treatment of central diabetes insipidus has not changed significantly in recent decades, and dDAVP and replacement of free water deficit remain the cornerstones of treatment. Oral dDAVP has replaced nasal dDAVP as a more reliable mode of treatment for chronic central diabetes insipidus. Hyponatraemia is a common side effect, occurring in one in four patients, and should be avoided by allowing a regular break from dDAVP to allow a resultant aquaresis. Hypernatraemia is less common, and typically occurs during hospitalization, when access to water is restricted, and in cases of adipsic DI. Management of adipsic DI can be challenging, and requires initial inpatient assessment to establish dose of dDAVP, daily fluid prescription, and eunatraemic weight which can guide day-to-day fluid targets in the long-term.

The prevalence and incidence of thyroid dysfunction in patients with diabetes - a longitudinal follow-up study.

BACKGROUND: Thyroid dysfunction (TD) occurs in 13.4% of diabetic patients, which has prompted recommendations for annual thyroid screening in patients with diabetes. However, recommendations for annual screening should be based on disease incidence rather than prevalence. METHODS: In 1997-1998, seven hundred and thirty patients (618 type 2 diabetes, 55% male; 112 type 1 diabetes, 47% male) were sequentially screened for TD. The 639 patients with normal thyroid function were followed from 1999 to 2006, with annual thyroid function tests. RESULTS: A total of 21/112 (19%) with type 1 diabetes (T1DM) and 70/618 (11%) with type 2 diabetes (T2DM) had TD. TD was more frequent in females (p < 0.05) and T1DM (p = 0.04). The mean annual rate of conversion to abnormal tests was 2.1%. At 8 years, there were 100 new cases of TD representing 15.6% of the cohort (17 T1DM and 83 T2DM). TD was more frequent in females (p < 0.05), but there was no difference in the incidence of new TD between T1DM and T2DM (p = 0.39). CONCLUSIONS: Our data confirms the high prevalence of TD in diabetic patients, in concordance with the results from other series. We found only 25 treatable cases of new thyroid disease from 639 patients in the 8-year follow-up, less than 0.5% per year. The low incidence of treatable thyroid disease challenges the need for annual screening for thyroid abnormalities in patients with type 2 diabetes.