Is coeliac disease more prevalent in young adults with coexisting Type 1 diabetes mellitus and autoimmune thyroid disease compared with those with Type 1 diabetes mellitus alone?

AIM: It is known that patients with Type 1 diabetes mellitus are more prone to develop coeliac disease and that autoimmune thyroid disease occurs more frequently in patients with coeliac disease. We therefore assessed whether coeliac disease, either known or occult, occurs more frequently in young/middle aged adults with Type 1 diabetes and coexisting autoimmune thyroid dysfunction than in adults with Type 1 diabetes alone. METHODS: The prevalence of known coeliac disease was assessed in 509 (301 males, aged 16-55 years) patients with Type 1 diabetes, 28 (5.5%) of whom had treated autoimmune thyroid disease. In a second study 38 patients with Type 1 diabetes and coexisting autoimmune thyroid disease along with 112 patients with Type 1 diabetes alone were then screened for coeliac disease using serum IgA endomysial antibodies and IgA gliadin antibodies. RESULTS: Seven of the 509 patients (1.4%) had been diagnosed with coeliac disease and two of these had later developed autoimmune thyroid disease (both hypothyroid). The subsequent screening exercise found that one of the 38 patients with both Type 1 diabetes and thyroid disease had positive endomysial antibodies on screening. However, duodenal biopsy was negative for coeliac disease. There were two patients with positive endomysial antibodies in the group of 112 patients with diabetes only. Both had duodenal biopsy but only one was consistent with coeliac disease. CONCLUSION: The prevalence of known coeliac disease in this young adult Type 1 diabetes clinic in North-west England was 7/509 (1.4%). Two of these seven patients with coeliac disease were from the group of 28 who had autoimmune thyroid disease as well. Therefore we suggest that patients with known coeliac disease and Type 1 diabetes should be screened for autoimmune thyroid disease. The second screening study then found 3/150 (2%) to have a serological marker for coeliac disease. However, patients with both Type 1 diabetes and autoimmune thyroid disease were not more likely to have occult coeliac disease compared with those with Type 1 diabetes only.

Elderly people with hypothalamic-pituitary disease and untreated GH deficiency: clinical outcome, body composition, lipid profiles and quality of life after 2 years compared to controls.

OBJECTIVE: Elderly patients with GH deficiency (GHD) have significant impairments in multiple aspects of quality of life (QOL) but similar lipid profiles compared to age-matched control subjects. There are, however, no data on changes in these parameters with time. This study assessed the impact of untreated GHD over a period of 2 years in a group of elderly patients with hypothalamic-pituitary disease in relation to new illnesses and differences in body composition, circulating lipid profile levels and QOL. Control subjects were also followed for 2 years. SUBJECTS: Twenty-seven elderly patients (> 65 years) with hypothalamic-pituitary disorders and GHD (mean peak stimulated GH response 1.6 mIU/l, range 0.6--5.0) were studied initially. Two years later 21 (13 males) agreed to attend for reassessment. Mean age was then 72.7 +/- 5.04 years (range 67--85). Eighteen patients had pituitary tumours, three had craniopharyngiomas. Twenty-seven control subjects were studied at baseline and 17 (7 males) agreed to attend for reassessment. Mean age was then 75.9 +/- 6.97 years (range 67--88). METHODS: Weight, body mass index (BMI), total fat mass (FM) (bioelectrical impedance), serum IGF-1 and fasting lipid profile (total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol) were measured. QOL was assessed in both groups using five interviewer-administered self-rating questionnaires: the Nottingham Health Profile, Short Form-36, Hospital Anxiety and Depression Scale, Mental Fatigue Questionnaire and Life Fulfillment Scale. The GHD group also completed the Disease Impact Scale. RESULTS: Two of the 27 patients with GHD died during the 2-year follow-up (myocardial infarction and probable cerebrovascular accident). Four controls could not be traced but there were no deaths in the other 23. In the 21 GHD patients after 2 years, mean serum IGF-1 and BMI were unchanged (12.6 +/- 5.8 vs. 13.3 +/- 5.1 nmol/l, P = 0.5 and 28.3 +/- 4.3 vs. 29.1 +/- 4.2, P = 0.5, respectively) at the 2-year follow-up and there were no significant changes in the lipid profiles. However, there was a significant reduction in fat mass (31.7 +/- 11.2 vs. 28.5 +/- 10.9%, P = 0.04). In the 17 control subjects after 2 years, serum IGF-1 levels (17.2 +/- 4.0 vs. 15.7 +/- 5.6 nmol/l, P = 0.4), BMI and fat mass were unchanged. However, there was a significant fall in total cholesterol levels over the 2-year follow-up (6.3 +/- 0.9 vs. 5.7 +/- 0.9 mmol/l, P < 0.0001), although LDL cholesterol, triglycerides and HDL cholesterol were unchanged. Analysing the QOL data, the GHD patients had less energy (P < 0.05), more depression (P < 0.05), more pain (P < 0.05) and lower life fulfillment scores (P < 0.01) after 2 years. However, the control subjects also had less energy (P < 0.05), less vitality (P < 0.05) and lower self-esteem (P < 0.05), more depression (P < 0.05), worse mental health (P < 0.05), life fulfillment personal (P < 0.01), life fulfillment material (P < 0.02), physical functioning and role physical functioning (P < 0.05) after 2 years. Comparing the patients and controls at baseline, there were significant differences in IGF-1, BMI, FM, LDL cholesterol, personal life fulfillment, mental fatigue, general health and mental health. However, after 2 years, only BMI and depression scores were significantly different. CONCLUSION: These patients with untreated GHD did not have deterioration of body composition or lipid profiles when reassessed after a period of 2 years. In fact, fat mass fell. The control subjects did have a significant decrease in total cholesterol but no change in other lipids or body composition. Some quality of life domains did deteriorate in the patients with GHD. However, the control subjects also had worse quality of life scores after 2 years which were then little different from the GHD patients. These results raise doubts about the benefits of GH replacement in elderly people with GHD.

A hard thyroid mass due to plasma cell granuloma.

Plasma cell granuloma involving the thyroid is very rare. A 29-year-old man with type 1 diabetes mellitus presented with a one-week history of fever, sore throat, neck tenderness and dysphagia. Antibiotics were given but over the next two weeks a hard 8 cm mass in the left lobe of the thyroid developed. Fine needle aspiration was not diagnostic and surgical exploration revealed an inflammatory process arising from the left lobe of the thyroid involving the left sternothyroid muscle and parapharyngeal spaces. Histology of multiple biopsies showed plasma cell granuloma. Immunoperoxidase staining demonstrated the presence of IgG, IgM and IgA with predominance of IgG. The residual mass resolved and was impalpable after four weeks. Plasma cell granuloma should be suspected when there is a rapidly developing hard thyroid mass. Open biopsy/removal and histological confirmation are mandatory and residual disease may resolve within weeks.

Hydrocortisone replacement dosage influences intraocular pressure in patients with primary and secondary hypocortisolism.

BACKGROUND: It has been suggested that the variation of intraocular pressure (IOP) during the day follows the diurnal variation of serum cortisol. There is also a higher risk of ocular hypertension and glaucoma in patients taking excessive oral steroid treatment. We assessed whether different replacement doses of hydrocortisone (HC) influenced IOP. METHODS: Seventeen patients (six Addison's disease, 11 hypopituitarism; seven males) aged 24-58 years mean 42.7 years and 20 control subjects (nine males) aged 20--59 years mean 38.7 years were studied. On the first visit, the 17 patients had been taking HC replacement doses, 20 mg morning and 10 mg afternoon. Serum cortisol and IOP in both eyes (Goldmann applanation tonometer) were measured at 0900, 1100, 1300, 1500, 1700 hours with HC 20 mg taken after the 0900 h assessment. The dose of HC was then reduced to 10 mg morning and 10 mg afternoon for 1 week and the measurements were repeated in 16 patients, with HC 10 mg taken at 0900 h. RESULTS: In the patients the peak serum cortisol occurred at 1100 h after the 0900 h HC dose. Cortisol levels were significantly higher at 1100, 1300, 1500 and 1700 h after taking 20 mg compared to 10 mg HC. The mean (SEM) IOP (mmHg) was significantly higher after 20 mg HC compared with 10 mg HC at 1300 h: 14.7(0.6) v 13.1(0.6) (P = 0.004) and at 1500 h: 14.4(0.6) v 13.1(0.5) (P = 0.04). The total mean (SEM) daily IOP score was significantly higher after 20 mg HC compared with 10 mg HC: 14.5(0.3) v 13.5(0.3) (P = 0.0002). The total mean (SEM) daily IOP score after the 20 mg HC dose compared with the control subjects was: 14.5(0.3) v 13.7(0.3) (P = 0.08). CONCLUSION: Intraocular pressures during the day are influenced by the morning hydrocortisone replacement dosage with significantly higher intraocular pressure levels in the early afternoon following 20 mg compared with 10 mg. A morning hydrocortisone dose of 10 mg leads to a more physiological intraocular pressure profile during the day. These data support the view that a daily replacement dose of 30 mg hydrocortisone may be excessive.

Elderly people with hypothalamic-pituitary disease and growth hormone deficiency: lipid profiles, body composition and quality of life compared with control subjects.

OBJECTIVE: In healthy adults the secretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) declines with ageing and body composition alters, particularly with an increase in total body fat. In elderly people, hypothalamic-pituitary disease can cause GH deficiency (GHD), compared with age matched controls. This study aimed to clarify whether GHD in the elderly is associated with differences in body composition, circulating lipid levels and quality of life (QOL) compared with control subjects. SUBJECTS: Twenty-seven elderly patients (14 males, mean age 71 years, range 65-83) with hypothalamic-pituitary disorders (23 pituitary tumours) and GHD (mean (SD) peak stimulated GH response 1.6 mIU/l (1.03) range 0.6-5) were studied. Twenty-five patients had been treated surgically (six cranial surgery, 19 transsphenoidal) and eight patients had received external cranial irradiation. Twenty-seven control subjects (14 males, mean age 72 years, range 65-86) were also studied. METHODS: Weight, body mass index (BMI), total fat mass (FM, bioelectrical impedance), waist to hip ratio (WHR), serum IGF-1, fasting blood glucose and lipid profile were measured. QOL was assessed in both groups using five interviewer administered self-rating questionnaires: The Nottingham Health Profile, Short-Form 36, Hospital Anxiety and Depression Scale, Mental Fatigue Questionnaire and Life Fulfilment Scale. The GHD group also completed the Disease Impact Scale. RESULTS: The data (mean (SD)) from males and females were analyzed separately. The male patients had a higher BMI than controls, 28.9(4.5) vs. 25.2(2.3) kg/m2 (P = 0.01) but the BMI in the female patients and controls was similar. In the female patients compared with the controls, FM was higher 39. 4(6) vs. 33.1(8.3) % (P = 0.02), WHR was also higher 0.9(0.08) vs. 0. 83(0.09) (P = 0.03) and serum IGF-1 levels were lower 10.8(6.4) vs. 18.2(6.5) nmol/l (P = 0.01). However, in the male patients, FM, WHR and IGF-1 levels were similar to the controls. Fasting blood glucose was similar in both male and female patients and the controls. Two female patients and one male control subject were taking lipid-lowering agents and were therefore excluded from the analysis of lipid profiles. Total cholesterol, triglyceride, LDL cholesterol, HDL cholesterol and total cholesterol/HDL cholesterol ratio were not significantly different for both male and female patients compared with the controls. The 27 patients with GHD reported significantly less energy (P < 0.05), mobility (P < 0.05) and personal life fulfillment (P < 0.01) than the 27 controls. There were significantly more problems with emotional reaction (P < 0.01), social isolation (P < 0.05) and mental fatigue (P < 0.05). Additionally the GHD group reported more impairment in areas of social functioning (P < 0.05), general health (P < 0.05) and mental health (P < 0.05). The GHD group reported a modest degree of disease impact (mean score of 14.1). There were no significant differences in the domains of material life fulfillment, pain, sleep, physical functioning, vitality, anxiety, depression, self-esteem or role physical functioning compared with the controls. CONCLUSION: Compared with control subjects, the elderly female patients with hypothalamic-pituitary disease and GHD had a significantly higher total fat mass, with the WHR indicating a more central fat distribution and lower female serum IGF-1 levels. In contrast, elderly male patients had similar total fat mass, WHR and IGF-1 levels compared to the controls. There were no significant differences in the lipid profiles between male or female patients compared to controls. However, many of the male patients were receiving androgen replacement which might have influenced these results. Low HDL cholesterol concentrations are probably a better predictor of future cardiovascular disease than raised LDL cholesterol levels in the elderly population and these were similar in patients and controls for both

Recurrent encephalopathy and generalised seizures associated with relapses of thyrotoxicosis.

Seizures or encephalopathy associated with thyrotoxicosis are very rare. A 30-year-old man with thyrotoxicosis and strongly positive thyroid antibodies presented with generalised seizures preceded by an encephalopathic illness of a few days duration. CSF protein was raised and EEG showed bilateral slowing of activity. Antithyroid drug treatment rendered him biochemically euthyroid, his cognitive state returned to normal and his seizures stopped. Subsequently he had a recurrence of both encephalopathy and seizures on two occasions, coinciding with relapses of the thyrotoxicosis. This supports the view that the hyperthyroid state caused this serious neurological condition. Treatment with 131I caused hypothyroidism and he has remained seizure free and well for six years on thyroxine replacement. Corticosteroids may have been helpful in the management of his encephalopathy.