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1. Anaemias of pregnancy are reviewed, noting that the common Fe deficiency anaemia is largely a social problem. 2. The aetiology; diagnosis and treatment of megaloblastic anaemia of pregnancy and the puerperium are discussed. 3. Three cases of this latter type of anaemia are recorded.

1. The incidence of diabetes mellitus in Ireland is of the order 1 per 860 of the population. 2. Irish diabetics display the usual tendency to develop the disease in the later decades of life. In the older age groups females outnumber males. 3. Amongst females who develop diabetes mellitus in later life, there is a high incidence of obesity and of high multiparity. 4. Pulmonary tuberculosis is particularly likely to develop in thin diabetics. This combination of diseases responds well to modern methods of treatment. 5. The problem of diabetes in pregnancy is the problem of foetal salvage and, this depends on good patient co-operation; careful control of the diabetes and, close liaison between physician and obstetrician, both of whom should have special experience of the problem. Delivery should take place in a fully equipped maternity hospital. 6. The degenerative vascular diseases are now the chief causes of death in diabetics.

FOUR cases of idiopathic hypoparathyroidism are presented. In three of these cases there was evidence of familial endocrinopathy (cases 2, 3, and 4) and in two (cases 3 and 4) there was evidence of multiple autoimmune endocrine disease. The diagnosis of idiopathic hypoparathyroidism and some interesting features of the disease and its treatment are discussed.

Seven hundred and thirty-six cases of juvenile-onset, insulin-dependent diabetes mellitus were studied, to investigate a possible relationship between seasonal incidence rates and a family history of diabetes mellitus of either type. Seasonal incidence was significantly affected by the presence or absence of a family history of diabetes of either type. Seasonal variation was present to a significant degree (p

Sixty-six insulin-dependent diabetic patients with normal visual acuity were studied (132 eyes). The mean age was 27.7 years with a mean duration of diabetes mellitus of 8.7 years. Their mean electro-oculogram ratio, Arden grating and Munsell-Farnsworth scores were markedly abnormal (p much less than 0.00001). Background retinopathy was present in 53 eyes (40.2%), abnormal Arden grating scores (greater than 82) in 70 eyes (53%), abnormal Farnsworth-Munsell 100-hue score (greater than 100) in 88 eyes (56.7%), and 29 eyes (22%) had an electro-oculogram ratio less than 160. These abnormalities of retinal function did not correlate with retinopathy and were not secondary to it. Smoking caused a significant deterioration in contrast sensitivity.

Many authorities are currently suggesting specific strategies for optimal obstetrical management of pregnant diabetic patients which involve early admission, frequent monitoring and a high Caesarean section rate. The author suggests that a more conservative approach may be indicated. In support of this contention, he cites from his personal experience of managing over 1,000 diabetic pregnancies during the past 34 years. As there were no therapeutic abortions, the series is consecutive and unmodified. There were no maternal deaths, and the perinatal loss during the 34-year period was 7.4%. In the years 1979-1984 the perinatal loss in 285 viables was 4.5%, and the Caesarean section rate was 25.9%. In 87 primigravidae, the Caesarean rate was 31%.

A patient who developed hyperparathyroidism and osteomalacia causing a pathological fracture of the neck of the femur, with development of a neuropathy, while on long term phenytoin and phenobarbitone treatment is described.

Summary Two sisters with diabetes mellitus and optic atrophy are described. One of them also has vasopressin responsive diabetes insipidus. Both have diabetic cheiroarthropathy, an unusual deformity of the hands.

The clinical outcome of 141 consecutive diabetic pregnancies managed in the National Maternity Hospital between January 1, 1979, and October 31, 1982, is described. Patients with gestational diabetes were excluded. There were 12 spontaneous abortions, and the perinatal mortality in 129 viable pregnancies was 31/1000. The malformation rate was 6.4%. Significant perinatal morbidity occurred in 20% of infants. The incidence of cesarean section was 20%. Spontaneous labor after 38 weeks occurred in 30% because there was a deliberate policy to allow all uncomplicated pregnancies to continue to term. This policy had benefits for the infant as well as the mother because there was a notable reduction in neonatal morbidity. Possible explanations of high cesarean section rates in other centers are discussed.(Obstet Gynecol 62:279, 1983)

Seventy-seven pregnancies (79 infants) complicated by hyperthyroidism were seen at three Dublin Maternity Hospitals during a 25 year period. Hyperthyroidism was diagnosed following conception in 14 pregnancies. Treatment was with carbimazole alone in 73 pregnancies, in a usual dose of 5 to 10 mg daily. The total fetal loss was 15.2 per cent with a perinatal loss of 5.1 per cent. The perinatal loss in patients treated with carbimazole alone was 4.1 per cent (excluding one death due to congenital malformation). Four infants (5.1 per cent) had goitre and 57 (85.1 per cent) of the surviving infants were above the 25th centile for gestational age. Spontaneous premature labour occurred in 7 pregnancies (9.1 per cent). There was a relative excess of infants with a birth weight less than the 25th centile, of neonatal goitre and premature labour after pregnancy in which treatment was started following conception. Hyperthyroidism complicating pregnancy can be treated effectively with antithyroid drugs given alone and in the minimal effective dose.

Goitre is common and alterations in biochemical indices of thyroid function are invariable during pregnancy , but thyroid disease, of which hyperthyroidism is the most frequent (0,05% of 72,257 pregnancies at three Dublin Maternity Hospitals, 1979-81) is rare. Good results in terms of perinatal loss (4/112, 3.57%) has been achieved by one of us (MID) in 109 pregnancies using antithyroid drugs alone. Neonatal thyrotoxicosis occurs in one to two percent of babies born to mothers with thyroid disease. The condition is usually transient but a prolonged course may occur in up to 20 percent. Successful pregnancy is possible despite maternal hypothyroidism; three such pregnancies have been managed by one of us (MID). Clinical hyperthyroidism due to trophoblastic disease is very rare and is cured by evacuation of molar tissue. The course of thyroid cancer is not affected by pregnancy.

An adult patient is described with hepatomegaly and sea-blue histiocytes in the bone marrow. A diagnosis of cholesterol ester storage disease was established following enzyme and lipid analyses on liver biopsy and cultured skin fibroblasts. Acid esterase activity was deficient (approx. 5% of controls) in liver and fibroblasts using [14C]-triolein or 4-methylumbelliferyl palmitate as substrates. Cholesterol ester levels were raised about 70-fold in liver, whereas triglyceride levels were only marginally raised. Marked accumulation of cholesterol esters was also demonstrated in cultured fibroblasts. Clinically, the patient responded favourably to phenobarbitone treatment. However, this was not reflected in liver acid esterase or lipid levels.

CLASSIFICATION by cause provided the basis for appropriate adjustment in treatment of 30 insulin treated diabetics, e.g.

Twenty patients with primary idiopathic haemochromatosis were tissue typed. HLA-A3 and B7 were increased in frequency. The significance of these findings in relation to other studies is assessed.

SINCE 1976 the standard inpatient and outpatient service for diabetic patients at the Mater Hospital has been supplemented by a day centre facility incorporating education and management. We feel that the service could be improved further by the availability of a specialist nurse who would visit patients at their homes. A pilot study was carried out over a twelve month period and this paper details the benefits of such a service.

The speaker presents a personal experience extending from 1951 to August 19841,2 The series, which is composed of 1013 pregnancies (1034 infants) in 504 women with clinical diabetes, is unique in that it represents the experience of one physician and is consecutive and unmodified. There was no maternal death and the perinatal mortality has improved consistently over the years. That part of the series which relates to the period 1979 to August 1984 will be discussed in detail, showing how a policy of strict control of diabetes permits uncomplicated cases to go to term or later with beneficial effects on neonatal morbidity and a high rate of spontaneous labour and vaginal delivery. In 270 viable infants delivered since 1979 the perinatal loss was 4% (corrected for malformations = 3%) and the overall caesarean section rate 26%

A review of the outcome of treatment by subtotal thyroidectomy, radio-iodine and carbimazole of 837 patients with hyperthyroidism seen consecutively over the period 1954–78 inclusive is presented. The age and sex distribution, the male to female ratio, the ABO blood group distribution and the prevalence of pernicious anaemia and diabetes mellitus in these patients was also analysed. Life-table data showed that the five-year and ten-year cumulative relapse rates following a two-year course of carbimazole ( n = 162) were 56 per cent and 62 per cent; following surgery ( n = 266), 6 per cent and 10 per cent and following radio-iodine ( n = 43), 3 per cent and 14 per cent. Five-year and ten-year cumulative hypothyroid rates after surgery were 10 per cent and 18 per cent, and after radio-iodine 10 per cent and 30 per cent. Hypothyroidism did not occur after carbimazole therapy. Of 31 patients who took carbimazole for less than two years (mean 11 months, range 6–19 months), 91 per cent had relapsed at five years. Of 79 patients treated for longer than two years (mean 3.8 years, range 2½–14 years), relapse rates at five and eight years were 49 per cent and 62 per cent. Nine patients (3.4 per cent) suffered permanent vocal cord paralysis and five (1.9 per cent) had permanent hypocalcaemia. The male/female ratio was 9.9 to 1, with a peak female prevalence between 25 and 30 years and a peak male prevalence between 40 and 45 years. The ABO blood group distribution among patients did not differ significantly from the distniution in the general population ( x 2 = 13.4, p = 0.2). Forty-seven patients (5.6 per cent) had diabetes mellitus and thyrotoxicosis whilst two patients (0.23 per cent) had diabetes, thyrotoxicosis and pernicious anaemia.

The efficacy of our current educational programme for diabetic patients was assessed. Cognitive and behavioural tests were administered to 75 Type 1 (insulin-dependent) diabetic patients, aged less than or equal to 30 years attending the Diabetic Clinic of the Mater Misericordiae Hospital, Dublin, Ireland. An overall deficiency in knowledge was evident. Fifty-one patients responded incorrectly to greater than 20% of the items tested. Twenty-nine patients lacked the ability to communicate a simple understanding of diabetes. Whereas most (70 +) correctly identified the methodology of urinalysis, uncertainty was evident concerning appropriate action needed in response to such tests. Forty-nine did not know the significance of thirst and polyuria and 20 were unaware that hyperglycaemia could progress to coma. The ability to modify insulin dosage was poor as was the ability to use exchanges. Of patients aged greater than or equal to 20 years, those from the Dublin region scored better than did those from surrounding towns or rural areas, (r = 0.5; p less than 0.01). Regular out-patient attenders scored less well than non-attenders (r = 0.24; p less than 0.05) but had better glycosylated haemoglobin levels (r = 0.3; p less than 0.01). Gycosylated haemoglobin showed no significant correlation with level of knowledge held.

Summary Among a diabetic clinic population of 5,000 there were 113 patients (1.1%) with concurrent clinical thyroid dysfunction (56 hyperthyroid, 57 hypothyroid). Seventy-one (62.8%) of these patients were insulin-dependent and diabetes preceded thyroid disease in 85 (75.2%). Twenty patients were given carbimazole for two or more years and of these 15 (75%) relapsed, a percentage not significantly different from that seen in non-diabetic patients. The value of screening diabetic patients for evidence of thyroid dysfunction is discussed.

This propective study was undertaken to evaluate serial measurements of glycosylated haemoglobin (HbA1) as an index of control in diabetic pregnancy. Glucose and haemoglobin A1 were measured at weekly intervals throughout 88 pregnancies. Levels of HbA1 and glucose correlated significantly. Elevated HbA1 levels in the second and third trimester and postnatally were associated with hydramnios. Other obstetrical complications were too few to permit meaningful correlations. Smoking practice was associated with raised mean HbA1 levels in the first and second trimester. In patients of White’s Class A, smoking was strongly associated with lower birth weight and weight centile. Foetal loss (abortion, stillbirth) or malformation correlated significantly with the mean HbA1 overall and with the mean HbA1 in the second trimester. Although the number of neonatal complications pertaining to an individual baby correlated with the mean HbA1 overall and with the mean HbA1 in the third trimester neither neonatal hypoglycaemia nor hyperbilirubinemia showed a correlation. Levels of HbA1 correlated with skinfold thickness but not with baby weight. The value of HbA1 as an index of diabetic control in pregnancy is discussed.

Esophageal function in 20 subjects with diabetes mellitus was assessed using esophageal manometry, 24-hr ambulatory esophageal pH monitoring, and esophageal scintigraphy. Seven patients had abnormal esophageal manometric studies, and this abnormality was significantly associated with peripheral neuropathy. Almost half of the subjects studied demonstrated excessive gastroesophageal acid reflux, but there was no correlation between the likelihood of abnormal reflux and the presence of peripheral neuropathy. Esophageal scintigraphy was relatively insensitive in the detection of abnormal esophageal function in diabetics.

The distribution of HLA antigens in a group of Irish patients with hyperthyroidism was studied, in an attempt to define whether specific antigens were associated with relapse of the disease following medical therapy. The increase in HLA-B8 and DR3 found by others in this disease was confirmed, but no difference in HLA type was documented in 33 patients who had relapsed compared to 24 who had not relapsed. Forty-six per cent of the relapsed group were DR3 as against 45% of the non-relapsed group.

A review of the outcome of treatment by subtotal thyroidectomy, radio-iodine and carbimazole of 837 patients with hyperthyroidism seen consecutively over the period 1954--78 inclusive is presented. The age and sex distribution, the male to female ratio, the ABO blood group distribution and the prevalence of pernicious anaemia and diabetes mellitus in these patients was also analysed. Life-table data showed that the five-year and ten-year cumulative relapse rates following a two-year course of carbimazole (n = 162) were 56 per cent and 62 per cent; following surgery (n = 266), 6 per cent and 10 per cent and following radio-iodine (n = 43), 3 per cent and 14 per cent. Five-year and ten-year cumulative hypothyroid rates after surgery were 10 per cent and 18 per cent, and after radio-iodine 10 per cent and 30 per cent. Hypothyroidism did not occur after carbimazole therapy. Of 31 patients who took carbimazole for less than two years (mean 11 months, range 6--19 months), 91 per cent had relapsed at five years. Of 79 patients treated for longer than two years (mean 3.8 years, range 2 1/2--14 years), relapse rates at five and eight years were 49 per cent and 62 per cent. Nine patients (3.4 per cent) suffered permanent vocal cord paralysis and five (1.9 per cent) had permanent hypocalcaemia. The male/female ratio was 9.9 to 1, with a peak female prevalence between 25 and 30 years and a peak male prevalence between 40 and 45 years. The ABO blood group distribution among patients did not differ significantly from the distribution in the general population (chi 2 = 13.4, p = 0.2). Forty-seven patients (5.6 per cent) had diabetes mellitus and thyrotoxicosis whilst two patients (0.23 per cent) had diabetes, thyrotoxicosis and pernicious anaemia.

Early recognition of Reye’s syndrome is important as prompt treatment may reduce morbidity and mortality. We report a case where the syndrome presented as ketoacidosis in a known diabetic.

Master, Colleagues, Ladies and Gentlemen, I am grateful for the honour you have done me in inviting me to give the Ninian Falkiner Memorial Lecture for 1982.