Haruhiko Isotani

Hypoparathyroidism and insulin‐dependent diabetes mellitus in a patient with Kearns–Sayre syndrome harbouring a mitochondrial DNA deletion

We report a 17‐year‐old girl with short stature, external ophthalmoplegia, atypical retinal pigmentary degeneration, sensorineural hearing loss, and cardiac conduction defect (Kearns–Sayre syndrome). A large‐scale deletion (6741 base pairs) in mitochondrial DNA was found in her muscle specimen. She also had insulin‐dependent diabetes mellitus (IDDM). On admission, her plasma glucose level was elevated at 31.0mmol/l with mild ketoacidosis, and haemoglobinA1c elevated at 16.5%. After improvement of diabetic ketoacidosis, she was placed on insulin 24–30 units/day despite her small body weight of 25 kg. There was reduced excretion of urinary C‐peptide at 3.97 nmol/day. In addition, she had idiopathic hypoparathyroidism with a serum calcium level of 2.15 mmol/l, phosphate 1.7 mmol/l, and intact PTH below 10 ng/l. Human leucocyte associated antigen typing showed A24, A26; B54, B61; CW1, CW3; DR8, DR14; DQ1 and DQ3, suggesting that the presence of HLA‐A24 and CW3 antigen contributed to the association of IDDM and hypoparathyroidism, similar to Japanese patients with polyglandular autoimmune syndrome, complicated by hypoparathyroidism and IDDM. We suggest that a genetic linkage, as well as mitochondrial dysfunction, may be responsible for the association of the two disease states. This is an extremely rare case of Kearns–Sayre syndrome, presenting in association with IDDM and idiopathic hypoparathyroidism.

DEVELOPMENT OF HYPERTHYROIDISM FOLLOWING PRIMARY HYPOTHYROIDISM: A CASE REPORT WITH CHANGES IN THYROID‐RELATED ANTIBODIES

We report a 48‐year‐old woman who developed hyperthyroidism following primary hypothyroidism. The serum T4 level was initially low and serum TSH level was high with clinical signs of hypothyroidism. The thyroid gland was not enlarged. Therapy with L‐T4 was started. Three years later she developed hyperthyroidism; serum free T4 increased to 29–1 pmol/l after cessation of L‐T4 therapy. The 123I thyroid uptake was increased with no suppression by exogenous T3. When she was hypothyroid, the activity of thyroid stimulating antibodies (TSAb) in serum measured by cyclic AMP production in cultured porcine thyroid cells were negative at 93.4% (normal < 140%), while thyroid stimulation‐blocking antibodies (TSBAb) determined by inhibition of TSH‐induced cyclic AMP increase were positive at 96.1% (normal < 40%). When hyperthyroidism subsequently occurred, TSBAb became negative (30.%), while TSAb became positive (163.3%). The findings indicate that hypothyroidism due to the potent TSBAb activity is not always persistent, but can be changed when various types of thyroid‐relating antibodies change in the course of the disease.

Pulmonary diffusing capacity, serum angiotensin-converting enzyme activity and the angiotensin-converting enzyme gene in Japanese non-insulin-dependent diabetes mellitus patients

We investigated the independent change in pulmonary diffusing capacity (DLCO) as one manifestation of pulmonary microangiopathy and to analyze the correlation between DLCO and serum ACE. We also examined the association between DLCO and the ACE genes. We examined pulmonary functions, especially %DLCO/VA (DLCO corrected by alveolar volume, percent predicted) in 54 NIDDM patients and 34 age-matched normal control subjects. Subjects were subdivided according to the degree of retinopathy. Serum ACE level was assayed by a colorimetric method in 54 patients and an insertion/deletion polymorphism in the ACE gene was amplified using the polymerase chain reaction in 52 of the 54 patients. There was a significant reduction of %DLCO/VA (percent predicted P < 0.05) in diabetic patients. In the proliferative retinopathy (PDR) group. %DLCO/VA was significantly (P < 0.05) lower than in the no diabetic retinopathy (NDR) and simple diabetic retinopathy (SDR) groups. Although the levels of serum ACE were within normal ranges in all diabetic groups, %DLCO/VA was negatively correlated with serum ACE values (r = 0.49, P < 0.0002, y = -1.4x + 109.3). Differences among DD, ID and II type of the ACE gene, with respect to the incidence of abnormal values of each clinical parameter, were not significant. DLCO was significantly reduced in patients with PDR and the serum ACE was significantly related to impaired DLCO. Our study suggests the existence of microangiopathic involvement of pulmonary vessels in NIDDM patients.

McCune-Albright Syndrome Associated with Non-Autoimmune Type of Hyperthyroidism with Development of Thyrotoxic Crisis

We report on a patient having McCune-Albright syndrome (MAS) associated with non-autoimmune hyperthyroidism associated with thyrotoxic crisis. Polyostotic fibrous dysplasia developed at age 8, and café-au-lait pigmentation was noted on the skin. At age 18, he developed hyperthyroidism with multiple adenomatous changes. The hyperthyroidism had been controlled with an antithyroid drug, but the antithyroid medication was discontinued by the patient at age 23. One year later, thyrotoxic crisis developed with fever, convulsions and loss of consciousness. Thyroid function tests showed serum concentrations of free T4 of 5.1 ng/dl, and serum TSH of <0.1 μU/ml. Serum thyroglobulin concentrations were markedly increased (1,280 ng/ml). Three major thyroid-related autoantibodies (TSH receptor antibody, antithyroglobulin, and antimicrosomal antibodies) were not detected in serum. Serum GH concentrations were increased, and not suppressed by the glucose tolerance test, but increased paradoxically by TRH. The thyrotoxic crisis was ameliorated by treatment with a β-adrenergic receptor-blocking agent, glucocoroticoid, iodine, antithyroid drug, and antibiotics. The cause of thyroidal defect in our patient is not considered to be autoimmune hyperthyroidism, but hyperthyroidism due to constitutive activation of Gsα by inhibition of its GTPase. This paper describes, as far as we know, the first case of MAS associated with thyrotoxic crisis. Because hyperthyroidism in this patient recurred quickly after discontinuation of the antithyroid drug, the mode of treatment for MAS-associated hyperthyroidism appears to be total surgical ablation or repetitive radioiodine therapy.

Diabetic ketoacidosis associated with the pheochromocytoma of youth

We report a case of diabetic ketoacidosis (DKA) associated with pheochromocytoma in a college student of 22 years of age who was admitted to hospital because of hyperglycemia and hypertension with palpitations and subsequently was found to have an adrenalin and noradrenalin secreting pheochromocytoma. A diagnosis was made and the patients impaired glucose tolerance and hypertension improved by tumor excision. This is the first reported case of a noradrenalin-predominant pheochromocytoma with associated DKA. Although DKA has been thought not to occur with pheochromocytoma, the possible cause of DKA associated with pheochromocytoma is now described. It is important to point out, as a clinical manager, that severe hypertension is a very unusual concomitant of DKA in young people and is the main indication for further examination.

Oval pupil in patients with diabetes mellitus : examination by measurement of the dark-adapted pupillary area and pupillary light reflex

Determination of the dark-adapted pupillary area (DAPA) by infrared photography revealed that some diabetic patients show corectopia (oval pupil) in addition to the small DAPA as pupillary abnormalities. The prevalence and clinical details of oval pupil were compared between diabetic patients and healthy subjects. Pupillary light reflexes were also analyzed with an infrared videopupillography in some of the diabetic patients. The healthy subjects were examined for the influence of age on the ratio of the pupillary diameter of the major and minor axes. The ratio was 1.04 +/- 0.02 (mean +/- S.D.) in the healthy subjects, and cases in which the ratio was +2 S.D. or higher than the mean ratio were defined as oval pupil. Oval pupil was observed in 21 (24%) of 86 diabetic patients, and was correlated with heart rate variation (P < 0.05) and DAPA (P < 0.01), which represent an autonomic dysfunction. Quantitative analysis of pupillary light reflexes with an infrared videopupillography revealed that the dark-adapted pupillary area before photic stimulation (P < 0.01) and the maximum %-velocity of constriction (P < 0.05) were significantly less in the oval pupil group than in the round pupil group. Cranial magnetic resonance imaging revealed no abnormalities in the oval pupil group. From these results, a peripheral autonomic disorder was implicated in the etiology of oval pupils in diabetic patients.

Acute Cerebellar Ataxia with an MRI Abnormality: A Sequential Imaging Study

Introduction Acute cerebellar ataxia (ACA), or acute cerebellitis, is a benign disease occurring with or after a nonspecific viral infection and generally has a good prognosis [1, 2]. ACA occurs most commonly in young children, and in the majority of cases, cerebrospinal fluid (CSF) and neuroimaging analysis are normal. Serial MRI findings have been reported in single-case studies in children [3, 4]. We report a sequential study of MRI in adult with ACA.

Insulin-dependent diabetes mellitus in which glycemic control was improved during pregnancy but deteriorated after delivery with the occurrence of postpartum thyrotoxicosis: a case report

We report a patient, a twin, with diabetes mellitus whose hyperglycemic state fluctuated during the course of the pregnancy and the subsequent delivery. She was diagnosed as having slowly progressive IDDM because of her clinical course and the findings of serum positive ICA/CF, positive HLA-DR4 and disconcordance of diabetes mellitus with her identical twin. Insulin therapy was not initially needed in the first two years because the endogenous insulin secretion was not completely reduced. After two years of insulin therapy the patient became pregnant. Her glycemic control was remarkably improved without changes in dietary intake and insulin dosage. After delivery glycemic control deteriorated after delivery with the occurrence of postpartum thyroiditis. Urinary excretion of CPR was increased during pregnancy but decreased after delivery. ICA/CF in serum were persistently detected in the whole observation period. It seems that the improved glycemic control during pregnancy was caused by the reduction in the autoimmune reaction and the deterioration in glycemic control during the postpartum period was induced by the acceleration of the autoimmune reaction by the same mechanism of postpartum autoimmune thyroiditis.

Measurement of GAD Antibody and HLA Antigens in Classification of Diabetes

Since acute-onset insulin-dependent diabetes mellitus (IDDM) usually demonstrates a greater number of HLA antigens related to IDDM than slowly progressive IDDM (SPIDDM), the type of diabetes may be affected by a dosage effect of HLA antigens. The purpose of this study is to elucidate the dosage effect of HLA antigens in modifying the type of diabetes. We assayed antibodies to glutamic acid decarboxylase (GADab) in 253 non-insulin-dependent diabetes mellits (NIDDM) patients and 17 IDDM patients. We assayed HLA antigens (class I A, B, C antigens, class II DR, DQ antigens) in 7 of 8 GADab-positive NIDDM patients and 3 GADab-positive acute-onset IDDM patients, whose disease etiologies may be related to the background of autoimmunity. We tried to score the association of HLA antigens with IDDM as positive or negative in each patient. If the patients had one HLA antigen related to IDDM, they were given one point. If they had one HLA antigen showing a negative association with IDDM, one point was subtracted from the score. HLA scores of GADab-positive patients with NIDDM tended to have a lower score, but exceptionally there were a few higher HLA scores among NIDDM patients. Both GADab-positive and negative IDDM patients tended to have higher HLA scores. Our results suggest that measurement of HLA antigens as well as GADab can be of clinical value in predicting the type of diabetes. Moreover, it may be possible to detect patients who should receive insulin during the early stage of GADab-positive NIDDM.