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Prolactin and thyrotrophin response to thyrotrophin-releasing hormone in growth hormone deficiency.

Basal and thyroid-releasing hormone-stimulated (200 micrograms/m2) prolactin and thyroid-stimulating hormone (TSH) levels were measured in 31 patients with hypopituitarism (13 isolated growth-hormone deficiencies and 18 multiple pituitary hormone deficiencies). The results were compared with the prolactin response in 76 healthy prepubertal children. Normal prolactin concentrations were found in 13 patients whereas 11 had increased levels. TSH levels were either normal or increased in patients who were considered to have hypothalamic disorders. Decreased prolactin response was present in 7 children, 6 of whom had multiple pituitary deficiencies. Their TSH response was decreased as well, indicating pituitary failure. There was good overall correlation of peak prolactin with peak, TSH concentrations. Some patients with 'isolated' growth hormone deficiency had an abnormal prolactin response indicating an additional hormonal deficiency. All patients with low levels of serum thyroxine had abnormal prolactin or TSH levels, high in some, low in others. Two euthyroid patients with increased prolactin stimulation became hypothyroid during treatment with growth hormones, thus questioning whether prolactin is a more sensitive indicator of early thyroid insufficiency than thyroxine or TSH levels.

Adolescent↗

Cushing's syndrome, growth impairment, and occult adrenal suppression associated with intranasal steroids.

We have previously described iatrogenic Cushing's syndrome secondary to intranasal steroids. This report further highlights the potential deleterious effects of intranasal steroids. Nine cases (including the original two cases) are reviewed to show the varied clinical manifestations of adrenal suppression caused by intranasal steroids. Four presented with Cushing's syndrome, three with growth failure, while two asymptomatic patients were discovered in the course of pituitary function testing. Four children had dysmorphic syndromes--Down's, Treacher-Collins, CHARGE association, and campomelic dysplasia--reflecting the vulnerability of such children to ENT problems, together with the difficulty of interpreting steroid induced growth failure in this context. Adrenal suppression was seen not only with betamethasone but also with budesonide, beclomethasone and flunisolide nasal preparations. A careful enquiry as to the use of intranasal steroids should be routine in children presenting with unexplained growth failure or Cushing's syndrome. Particular vigilance/awareness is required in children with dysmorphic syndromes.

Administration, Intranasal↗

Pituitary function with a solitary intrasellar plasmacytoma.

A solitary intrasellar plasmacytoma with marked pituitary fossa destruction and yet near normal pituitary gland function is described. We suggest that a minimal disturbance of endocrine function together with a radiologically abnormal pituitary fossa indicates that the primary lesion may lie outside the pituitary fossa.

Aged↗

Chronic hypernatraemia and hypothermia following subarachnoid haemorrhage.

We describe a 30 year old man who developed chronic adipsic hypernatraemia and hypothermia following a subarachnoid haemorrhage from an anterior communicating artery aneurysm. Anterior pituitary function tests were normal. Hypothermia was demonstrated over 4 years with loss of the ability to control heat conservation despite body temperatures as low as 30 degrees C. He failed to experience thirst despite plasma sodium concentrations of up to 187 nmol/l and plasma osmolalities of up to 397 mOsm/kg. The slope of the plasma vasopressin-plasma osmolality curve indicated loss of the osmoreceptor. There was an absent vasopressin response to insulin-induced hypoglycaemia but a normal response to apomorphine. The apomorphine-stimulated immunoreactive vasopressin was shown to behave identically to the synthetic peptide on HPLC and was bioactive.

Adult↗

Thickened pituitary stalk on magnetic resonance imaging in children with central diabetes insipidus.

Magnetic resonance imaging (MRI) has revealed isolated pituitary stalk thickening (PST) in certain cases of idiopathic or secondary central diabetes insipidus (DI) due to infiltrative processes. Twenty-six children with DI and PST underwent cerebral MRI at the age of 8 +/- 4 years and were followed (n = 25) by clinical and MRI evaluation for 5.5 +/- 3.6 and 3.0 +/- 2 years, respectively, but given no treatment other than hormonal substitutive therapy. Patients were subdivided into groups according to the etiology of the DI: germinoma (n = 4), Langerhans' histiocytosis (n = 5) or 'idiopathic' DI with PST (n = 17). Complete anterior pituitary evaluation in 24 of the 26 patients revealed that 14 children were suffering from associated growth hormone deficiency and 7 had multiple hormone deficiencies. At the first MRI evaluation, pituitary stalk enlargement varied from 2.2 to 9.0 mm. The anterior pituitary gland was found to be normal (n = 12), small (n = 8) or enlarged (n = 6). At the final evaluation, a change in MRI features had occurred in 16 patients: morphological and/or signal changes in the PST (n = 16; 6 of whom showed an increase in PST) and changes in anterior pituitary gland size (n = 8; 3 of whom had increased and 5 had decreased). The presence of a growing suprasellar mass with a progressively enlarging pituitary stalk was demonstrated in the 6 patients who had shown increased pituitary stalk enlargement 1.8 +/- 1.6 years after the first MRI. In 4 of these patients, a diagnosis of germinoma was made 1.3 +/- 0.6 years after PST identification by MRI at the onset of DI, but the other 2 patients showing a suprasellar mass were still categorized as 'idiopathic' at the final clinical evaluation performed 7.8 and 12.3 years after DI onset. In 10 patients (all but 1 with Langerhans' histiocytosis, showing 'idiopathic' DI) the pituitary stalk enlargement was diminished after 2.0 +/- 1.9 years of MRI follow-up, and there was a complete reversal of pituitary stalk enlargement in 5 patients. We conclude that the natural history of 'idiopathic' isolated central DI with PST is unpredictable. Although germinoma should always be considered during the first 3 years of follow-up in patients presenting isolated DI with PST by repeated investigations every 3-6 months, it remains an infrequent etiology, affecting only 15% of cases in our study.

Adolescent↗

The endocrine outcome after surgical removal of craniopharyngiomas.

The postoperative course of children undergoing surgery for craniopharyngioma was reviewed. Typically they were below height at presentation. All had an attempt at radical surgical resection of the tumor. Most developed diabetes insipidus in the postoperative period, which was permanent in all but 1 child. 94% required thyroid replacement therapy, and sex steroids were administered in 100% when they reached the age of puberty. 91% required maintenance corticosteroids. 54% required growth hormone replacement, but some children showed continued growth despite apparent growth hormone deficiency. Postoperative obesity develops in one half of patients, and may be improved with administration of growth hormone; a controlled trial is underway.

Adolescent↗

An approach to radical excision of craniopharyngioma by the temporal route.

Attempts at radical excision of craniopharyngioma has been made increasingly possible by the advent of neuroradiological imaging and the use of microscopic technique. Between 1977 and 1993, 62 patients of The National Hospital for Neurology and Neurosurgery, London, have undergone surgical excision of craniopharyngioma by the temporal route, with a small anterior temporal resection. Surgical mortality was 4%. Forty-eight patients (76%) remain well on average follow-up of 34 months. Twelve percent had major complications (hypothalamic damage, subdural haematoma, scalp collections requiring shunt drainage). There were four recurrences in patients where the initial operations were considered as complete microscopic excision. Maximal control of tumour recurrence by removal of all tumour accessible and visible to the surgical microscope is best achieved by radical excision at the first operation.

Adolescent↗

Craniopharyngioma: endocrine sequelae of treatment.

Following complete surgical resection of a craniopharyngioma, combined anterior and posterior pituitary dysfunction is present in the majority of patients. Moreover, up to three-quarters of the patients will have deficits of four or more hormones. Postsurgery, obesity is common and can be part of a clinical syndrome which includes hyperphagia and normal growth despite GH deficiency. Radiotherapy with or without conservative surgery is associated with fewer endocrine disturbances. Normal growth and sexual development should be possible in most patients with the use of appropriate hormonal substitution therapy.

Child↗

Secretion of melanocyte-stimulating hormone and adrenocorticotropin from transplanted pituitary pars intermedia in stressed and nonstressed rats.

Rats bearing kidney grafts of the pituitary pars intermedia were divided into three groups: unstressed, acutely stressed, and chronically stressed. Corresponding sham-operated rats were used for comparisons. Twenty days after grafting, the rats were sacrificed and alpha-melanocyte-stimulating hormone (alpha-MSH), adrenocorticotropin (ACTH), and corticosterone were estimated in plasma. The adrenal/body weight ratio and DNA content of the glands were also investigated. The following results were obtained: MSH was found not to be increased in unstressed rats, but it was in grafted animals subjected to acute and chronic swimming stress. ACTH and corticosterone rose in all three groups. Adrenal/body weight ratio and DNA content increased only in grafted chronically stressed rats. Moreover, plasma corticosterone was found higher in grafted hypophysectomized rats than in non-grafted hypophysectomized animals. Administration of ergocryptine to nonstressed grafted rats induced a decrease in the blood content of ACTH and MSH, indicating that the grafts were the source of a part of the circulating ACTH. On the other hand, the fall in MSH levels could show the effect of the drug upon the pars intermedia. Comparison of the ratios of both hormones released in incubations showed that grafts secreted more ACTH than MSH; on the other hand, when intact neurointermediate lobes were incubated, MSH predominated over ACTH. For the first time it is demonstrated that the pars intermedia can secrete ACTH in vivo. Nevertheless, the ability to secrete this hormone is not a property of normal intact pars intermedia, but it manifests in the transplantations probably due to the overactivity of light cells induced by chronic stoppage of dopaminergic inhibition.

Adrenocorticotropic Hormone↗