B. di Natale

Familial XX true hermaphroditism and the H-Y antigen

SummaryTwo 46,XX sibs, one of female, one of male gender, and both with ambiguous external genitalia and ovotestis, were H-Y positive. The mother was H-Y negative. It is assumed that the underlying mutation was transmitted by the father, resulting in an autosomal dominant mode of inheritance. The common origin and the nature of the mutation leading to XX sex reversal are discussed.

Growth hormone deficiency in children: Role of magnetic resonance imaging in assessing aetiopathogenesis and prognosis in idiopathic hypopituitarism

To search for the presence of morphostructural abnormalities of the hypothalamus-pituitary region in growth hormone deficient (GHD) children magnetic resonance imaging (MRI) was performed in 30 GHD patients (age 10.09±3.5 years) and in 15 healthy agematched controls. MRI demonstrated a significantly small sella and pituitary volume compared to controls and normal literatures values. In 20 patients the structures were extremely small and an abnormal development of the pituitary stalk was observed, and in 18 of these patients the bright spot indicating the neurohypophysis was dislocated to the distal part of the mal-developed stalk, although these children had a normal fluid balance. From a functional point of view hypothalamus and pituitary defects were equally distributed between the two morphological groups. The patients with multiple endocrine defects had the smallest pituitary volume and abnormal stalk. A possible pathogenetic role of perinatal trauma or dysembriogenic events are discussed. A careful follow up of patients with isolated GHD presenting MRI abnormalities of the pituitary is suggested for the possible evolution in panhypopituitarism.

Ventilatory Volumes, Flow Rates, Transfer Factor and Its Components (Membrane Component, Capillary Volume) in Obese Adults and Children

We have studied the ventilatory volumes, flow rates, transfer factor and its components (membrane component and capillary volume) in 19 women and 23 children with moderate obesity. The adults showed restrictive defects, but the pulmonary volumes of children were within normal range. Peak flow, flows at 75 and 50% forced expiratory volume, in two groups, normalized for the forced expiratory volume, did not differ between the two groups. The transfer factor was reduced in adults, because of reduction of the alveolar volume, the membrane component was low in both groups; transfer factor and membrane component normalized for functional residual capacity were not different between the two groups. The capillary volume was greater in children than adults, because the excess body weight was greater for the children. In simple obesity, the main alteration is the decrease of distensibility of the chest wall that becomes worse as time goes on and is the cause for the alterations in ventilatory volume, flow and transfer factor.

Effect of Somatostatin on Blood Sugar, Plasma Growth Hormone, and Glucagon Levels in Diabetic Children

In nine children with clinically overt insulin-dependent diabetes mellitus the authors injected cyclic somatostatin (3 mug./kg. bolus, followed by infusion of 13 mug./kg. in 60 minutes) and measured blood glucose, plasma growth hormone, and glucagon concentrations throughout the infusion. The rapid administration produced no significant changes of these parameters. With the prolonged infusion there was a significant reduction of blood glucose from a mean of 148 ± 19.7 to a mean of 88.5 ± 18.1 mg./100 ml. (P < 0.005) and of plasma glucagon from a basal mean of 33.3 ± 2.4 to a minimum mean of 22.1 ± 1.7 pg./ml. (P < 0.01). There was a statistically significant correlation between the two parameters (0.01 < P < 0.05). Plasma GH values also diminished during the infusion, but the reduction was not statistically significant. These results show that somatostatin lowers blood glucose concentrations as a secondary effect of inhibition of glucagon secretion. Somatostatin is not suitable for therapy in diabetes. We speculate that a similar substance with a more prolonged and specific action on glucagon might prove of practical value in the treatment of diabetes mellitus.

Bone mineral metabolism and thyroid replacement therapy in congenital hypothyroid infants and young children

Impairment of calcium metabolism and low bone density have been found in hypothyroid adults. We investigated the effect of thyroid replacement therapy on calcium metabolism and bone mineralization in congenital hypothyroid (CH) infants and children. One hundred and 16 Caucasian CH consecutive patients were studied and were grouped according to their age: 23 patients at diagnosis, 20 at 3 mo, 24 at 6 mo, 25 at 12 mo and 24 at 36 mo. Thyroid replacement therapy was started at an initial dose of 6–8 μg/kg/day of L-thyroxine, and then decreased progressively. Calcium, phosphorus, magnesium, alkaline phosphatase (AP), parathyroid hormone (PTH) and osteocalcin (BGP) were measured as calcium metabolism indices. Bone mineral content (BMC) was measured at the mid-portion of the right radius AP, PTH and BGP concentrations were significantly higher in subjects at 3 mo of age (p<0.05). This rise coincided with the end of the period of maximum dosage of L-thyroxine. Mild asymptomatic hypercalcemia was observed in 20 patients. All the other indices did not differ between age groups. BMC values and BMC annual increment were not different from those calculated for age-matched controls. We found that L-thyroxine replacement therapy does not alter bone mineralization of CH infants and children. Only a transitory increase of osteoblastic function was observed after the first few months of therapy.

Tolerance of the oral Clonidine test in 75 pediatric patients

We evaluated the tolerance and effectiveness of the oral Clonidine test for GH in 75 children, 84% with hyposomia and 16% with other diseases. The test was well tolerated, since 97% of the examined children had no side effects with the exception of occasional drowsiness, pallor and myosis of short duration. Two of the children at the end of the test, had more severe symptoms 30 min after (deep asthenia, pallor and a further small blood pressure drop) which however, resolved after 4–6 h. No correlation was observed between the clinical picture and the drops in blood pressure and/or plasma cortisol in the children examined. We confirm the effectiveness of the Clonidine test in the release of GH since in our study we observed no negative false subnormal responses.

Persisting Functional Connection in Growth-Hormone-Deficient Patients with a Transected Stalk

Prolactin response after domperidone (DOM) stimulus was used to investigate the functional status of the hypothalamo-hypophyseal axis in 57 congenital growth-hormone-deficient (GHD) children with and without magnetic resonance imaging (MRI) abnormalities. Response to DOM was significantly lower in the GHD children compared with controls, using maximum peak (p < 0.0001), increase (p < 0.0001) or percentage increase (p < 0.05). The lowest values were observed in patients with hypophyseal stalk transection. Thus, the DOM test revealed reduced dopaminergic transmission in GHD subjects, more severe in the transected group, in whom, however, a response to the stimulus was still present. Therefore, it seems that a residual hypothalamo-hypophyseal connection is preserved even if it is not detectable with MRI.

Isolated glucocorticoid deficiency

A three-month-old boy with hypoglycemic episodes, feeding problems and hyperpigmentation is described. Hormone assays revealed elevated serum ACTH values and low levels of plasma Cortisol that did not rise after exogenous ACTH administration; blood pressure, serum electrolytes and earlier plasma aldosterone and renin activity were in the normal range. These data suggest a diagnosis of an isolated glucocorticoid deficiency, secondary to unresponsiveness to ACTH. Replacement therapy with glucocorticoids was highly effective. Despite replacement therapy, during follow-up he had an increase in basal plasma renin activity with aldosterone concentration normal. In our patient, a mineralcorticoid deficiency might eventually develop; therefore, the selective glucocorticoid deficiency might also be part of a progressive defect involving the glomerulosa too.

MUSCULAR EXERTION: A TEST OF PITUITARY FUNCTION IN CHILDREN

ABSTRACT: Garlaschi, C, Del Guercio, M. J., Di Natale, B., Caccamo, A. and Chiumello, G. (Department of Paediatrics, University of Milan, Italy). Muscular exertion: a test of pituitary function in children. Acta Paediatr Scand, 64:752, 1975.–The elevated level of growth hormone after moderate standardized physical exercise was compared with that induced by intravenous arginine infusion and by insulin induced hypoglycemia in children with normal pituitary function. Tests were performed on 49 prepubertal children (34 boys and 15 girls); in 42 cases the increase was significant for all three tests, in 5 cases the response was minimal after insulin stimulation but normal after arginine and physical exertion; in 1 case arginine produced no response but the other tests were positive; in 1 case there was a response to arginine but none to insulin or physical exertion. The results indicate that frequently more than one test is necessary for the diagnosis of normal pituitary function; physical exertion being a physiologic test, is simple to perform, acceptable to the children and without side effects. It appears the test of first choice because it can be used in patients seen ambulatorily, other tests being performed in case of doubt or negative response.